Gene Summary

Gene:ADIPOQ; adiponectin, C1Q and collagen domain containing
Summary:This gene is expressed in adipose tissue exclusively. It encodes a protein with similarity to collagens X and VIII and complement factor C1q. The encoded protein circulates in the plasma and is involved with metabolic and hormonal processes. Mutations in this gene are associated with adiponectin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Apr 2010]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Source:NCBIAccessed: 01 September, 2019


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Acute Lymphocytic Leukaemia
  • Resistin
  • Polycystic Ovary Syndrome
  • Leptin
  • Models, Genetic
  • Risk Assessment
  • Risk Factors
  • Obesity
  • Smoking
  • Stomach Cancer
  • Membrane Proteins
  • Odds Ratio
  • Messenger RNA
  • Receptors, Leptin
  • Software
  • Cancer Gene Expression Regulation
  • China
  • Adiponectin
  • Insulin Resistance
  • Single Nucleotide Polymorphism
  • Polymorphism
  • Adolescents
  • Alleles
  • Reproductive Techniques, Assisted
  • Colorectal Cancer
  • Chromosome 3
  • Genetic Variation
  • Breast Cancer
  • Genetic Association Studies
  • Ultrasonography
  • Case-Control Studies
  • Prostate Cancer
  • PubMed
  • Genotype
  • Biomarkers, Tumor
  • Cell Proliferation
  • Asian Continental Ancestry Group
  • Body Mass Index
  • United Kingdom
  • Genetic Predisposition
Tag cloud generated 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: ADIPOQ (cancer-related)

Ge Y, Long Y, Xiao S, et al.
CD38 affects the biological behavior and energy metabolism of nasopharyngeal carcinoma cells.
Int J Oncol. 2019; 54(2):585-599 [PubMed] Free Access to Full Article Related Publications
Nasopharyngeal carcinoma (NPC) is the most common malignant tumor type in Southern China and South‑East Asia. Cluster of differentiation (CD)38 is highly expressed in the human immune system and participates in the activation of T, natural killer and plasma cells mediated by CD2 and CD3 through synergistic action. CD38 is a type II transmembrane glycoprotein, which was observed to mediate diverse activities, including signal transduction, cell adhesion and cyclic ADP‑ribose synthesis. However, the significance of CD38 in NPC biological behavior and cellular energy metabolism has not been examined. In order to elucidate the effect of CD38 on the biological behavior of NPC cells, stable CD38‑overexpressed NPC cell lines were established. It was demonstrated that CD38 promoted NPC cell proliferation with Cell Counting Kit‑8 and colony formation assays. It was also indicated that CD38 inhibited cell senescence, and promoted cell metastasis. Furthermore, it was determined that CD38 promoted the conversion of cells to the S phase and decreased the content of reactive oxygen species and Ca2+. Additionally, cell metabolism assays demonstrated that CD38 increased the concentration of ATP, lactic acid, cyclic adenosine monophosphate and human ADP/acrp30 concentration in NPC cells. To investigate the possible mechanism, bioinformatics analysis and mass spectrometry technology was used to determine the most notably changing molecule and signaling pathways, and it was determined and verified that CD38 regulated the metabolic‑associated signaling pathways associated with tumor protein 53, hypoxia inducible factor‑1α and sirtuin 1. The present results indicated that CD38 may serve a carcinogenic role in NPC by regulating metabolic‑associated signaling pathways.

Liu Z, Wang Z, Hao C, et al.
Effects of ADIPOQ polymorphisms on PCOS risk: a meta-analysis.
Reprod Biol Endocrinol. 2018; 16(1):120 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Whether adiponectin (ADIPOQ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk.
METHODS: Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.
RESULTS: Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p = 0.02, OR = 0.77, 95%CI 0.62-0.95; allele model: p = 0.001, OR = 1.15, 95%CI 1.06-1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians.
CONCLUSIONS: Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.

Chun KA, Kocarnik JM, Hardikar SS, et al.
Leptin gene variants and colorectal cancer risk: Sex-specific associations.
PLoS One. 2018; 13(10):e0206519 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: High levels of serum leptin and low levels of serum adiponectin are strongly correlated with obesity, a well-established risk factor for colorectal cancer (CRC). Growing evidence suggests that dysregulation of leptin and adiponectin levels may play an etiological role in colorectal carcinogenesis. We evaluated 20 candidate variants in 4 genes previously shown to alter serum leptin and adiponectin levels for associations with obesity (BMI>30 kg/m2) and CRC risk.
METHODS: We analyzed 6,246 CRC cases and 7,714 population-based controls from 11 studies within the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations of each variant with obesity or CRC were evaluated using multivariate logistic regression models stratified by sex and adjusted for age, a study variable, and the first three principal components of genetic ancestry. Gene-specific False Discovery Rate (FDR)-adjusted p-values <0.05 denoted statistical significance.
RESULTS: Two variants in the leptin gene showed statistically significant associations with CRC among women: LEP rs2167270 (OR = 1.13, 95% CI: 1.06-1.21) and LEP rs4731426 (OR = 1.09, 95% CI: 1.02-1.17). These associations remained significant after adjustment for obesity, suggesting that leptin SNPs may influence CRC risk independent of obesity. We observed statistically significant interactions of the leptin variants with hormone replacement therapy (HRT) for CRC risk; these variant associations were strengthened when analyses were restricted to post-menopausal women with low estrogen exposure, as estimated by 'never use' of HRT and/or non-obese BMI. No variants were associated with CRC among men.
CONCLUSIONS: Leptin gene variants may exhibit sex-specific associations with CRC risk. Endogenous and exogenous estrogen exposure may modify the association between these variants, leptin levels, and CRC risk.

Feng Y, Sun T, Yu Y, et al.
MicroRNA-370 inhibits the proliferation, invasion and EMT of gastric cancer cells by directly targeting PAQR4.
J Pharmacol Sci. 2018; 138(2):96-106 [PubMed] Related Publications
It has been reported that PAQR4 (Progestin and AdipoQ Receptor 4) expression is closely associated with progression of many cancers and microRNA (miRNA) processing. However, the effects and its precise mechanisms of PAQR4 in gastric cancer (GC) have not been well clarified. Our study aimed to explore the interaction between PAQR4 and miR-370 in GC. In our study, we found that the miR-370 level was significantly down-regulated in GC tissues and cell lines, and the expression of PAQR4 was dramatically increased. Interestingly, the low miR-370 level was closely associated with up-regulated PAQR4 expression in GC tissues. Moreover, introduction of miR-370 dramatically suppressed proliferation, invasion and EMT of GC cells. Whereas, miR-370 knockdown increased the proliferation, invasion and EMT in GC cells. We demonstrated that miR-370 could directly target PAQR4 by using both bioinformatics analysis and luciferase reporter assay. In addition, PAQR4 silencing had the similar effects with miR-370 overexpression on GC cells. Overexpression of PAQR4 in GC cells partially reversed the inhibitory effects of miR-370 mimic. miR-370 inhibited cell proliferation, invasion and EMT of GC cells by directly down-regulating PAQR4 expression, and miR-370 targeting PAQR4 was responsible for inhibition of the proliferation, invasion and EMT of GC cells.

Huang BZ, Tsilidis KK, Smith MW, et al.
Polymorphisms in genes related to inflammation and obesity and colorectal adenoma risk.
Mol Carcinog. 2018; 57(10):1278-1288 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
We previously investigated the association between single nucleotide polymorphisms (SNPs) in genes related to obesity and inflammation and colorectal cancer in the CLUE II cohort. However, the relationships between these SNPs and colorectal adenomas have not been well evaluated. In a nested case-control study of 135 incident adenoma cases and 269 matched controls in the CLUE II cohort (1989-2000), we genotyped 17 candidate SNPs in 12 genes (PPARG, TCF7L2, ADIPOQ, LEP, IL10, CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and 19 tagSNPs in three genes (IL10, CRP, and TLR4). Conditional logistic regression was used to calculate odds ratios (OR) for adenomas (overall and by size, histology, location, number). Polymorphisms in the inflammatory-related genes CRP, ADIPOQ, IL6, and TLR4 were observed to be associated with adenoma risk. At rs1205 in CRP, T (minor allele) carriers had a higher risk (OR 1.67, 95%CI 1.07-2.60; reference: CC) of adenomas overall and adenomas with aggressive characteristics. At rs1201299 in ADIPOQ, the AC genotype had a higher risk (OR 1.58, 95%CI 1.00-2.49) of adenomas, while the minor AA genotype had a borderline inverse association (OR 0.44, 95%CI 0.18-1.08; reference: CC). At rs1800797 in IL6, the AA genotype had a borderline inverse association (OR 0.53, 95%CI 0.27-1.05; reference: GG). Three TLR4 tagSNPs (rs10116253, rs1927911, rs7873784) were associated with adenomas among obese participants. None of these SNPs were associated with colorectal cancer in our prior study in CLUE II, possibly suggesting a different genetic etiology for early colorectal neoplasia.

Choe EK, Yi JW, Chai YJ, Park KJ
Upregulation of the adipokine genes ADIPOR1 and SPP1 is related to poor survival outcomes in colorectal cancer.
J Surg Oncol. 2018; 117(8):1833-1840 [PubMed] Related Publications
BACKGROUND: Obesity is closely associated with colorectal cancer (CRC), but the underlying mechanism is unclear. We thus evaluated the expression of the adipokine gene family in CRC tissues and its clinicopathological implications.
METHODS: Correlations between the mRNA expression levels of the adipokine gene family (ADIPOQ, ADIPOR1/2, LEP, LEPR, RETN, RETNLB, RBP4, SFRP5, NAMPT, and SPP1) in CRC tissue and clinicopathologic factors were analyzed using data from The Cancer Genome Atlas database.
RESULTS: Tissue samples from 369 patients were analyzed, and 82 deaths occurred during follow-up (median, 670 days). Overall, mortality was associated with positive venous invasion, higher TNM stage, and increased ADIPOR1 (adiponectin receptor 1 gene) and SPP1 (secreted phosphoprotein gene 1) mRNA expression. Higher ADIPOR1 (odds ratio [OR]: 3.29, 95% confidence interval [CI]: 1.33-8.13) and SPP1 (OR: 2.31, 95%CI: 1.49-3.59) levels were independently associated with increased mortality. A Kaplan-Meier survival analysis showed shorter overall survival times in patients with higher ADIPOR1 (P = 0.006) and SPP1 (P < 0.001) expression.
CONCLUSIONS: Upregulation of ADIPOR1 and SPP1, among the adipokine gene family, in cancer tissue is associated with poor survival in CRC, suggesting a potential mechanism linking obesity and CRC. ADIPOR1 and SPP1 expression could become useful prognostic indicators after further validation.

Hsueh YM, Chen WJ, Lin YC, et al.
Adiponectin gene polymorphisms and obesity increase the susceptibility to arsenic-related renal cell carcinoma.
Toxicol Appl Pharmacol. 2018; 350:11-20 [PubMed] Related Publications
Our recent study found that high urinary total arsenic levels were associated with renal cell carcinoma (RCC). Recent studies demonstrated that low circulating adiponectin was related to RCC. The aim of the present study was to explore the relationship between adiponectin gene (ADIPOQ) polymorphisms and RCC and investigate whether individuals with an ADIPOQ risk genotype, obesity, and high urinary total arsenic levels have a modified odds ratio (OR) of RCC. A total of 389 RCC patients and 389 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Image-guided biopsy or surgical resection of renal tumors was performed to pathologically verify RCC. Genomic DNA was used to examine the genotypes of the ADIPOQ rs182052, ADIPOQ rs2241766, ADIPOQ rs1501299, and ADIPOQ rs1063539 SNPs by PCR-RFLP. HPLC-HG-AAS was used to measure the concentrations of urinary arsenic species. Participants with the ADIPOQ rs182052 G/A+A/A genotype had a significantly higher OR of RCC compared with those with the ADIPOQ rs182052 G/G genotype. The OR (95% confidence interval [CI]) was 1.70 (1.23-2.36). The OR of RCC for the combined effect of high urinary total arsenic levels and obesity, which was dose-dependent, in individuals with the ADIPOQ rs182052 G/A+A/A genotype was 9.33 (3.85-22.62). The present study found significant combined effects of obesity and the ADIPOQ rs182052 G/A+A/A genotype on the arsenic-related risk of RCC in a population with low arsenic exposure. Arsenic exposure, obesity, and the ADIPOQ rs182052 polymorphism could be predictors of a higher OR of RCC.

Czeczuga-Semeniuk E, Galar M, Jarząbek K, et al.
The preliminary association study of ADIPOQ, RBP4, and BCMO1 variants with polycystic ovary syndrome and with biochemical characteristics in a cohort of Polish women.
Adv Med Sci. 2018; 63(2):242-248 [PubMed] Related Publications
PURPOSE: We aimed to elucidate the frequency of the SNPs in the ADIPOQ, RBP4 and BCMO1genes in a population of Caucasian Polish women with polycystic ovary syndrome (PCOS), and to evaluate the possible associations between these variants and the susceptibility to PCOS. Additionally, the relationship of these polymorphisms to a clinical phenotype of this syndrome, and the concentrations of adipokines, were determined.
MATERIALS/METHODS: Clinical and biochemical profiles, DNA isolation and genotyping, and adipokine assays were performed in 294 PCOS women and 78 controls.
RESULTS: In a cohort of Polish women, for the genotype distribution and allele frequencies (minor allele frequency - MAF) proved that only the SNP rs1501299 in the gene ADIPOQ (P = 0.0010, OR = 0.41, 95% C.I.:0.24-0.70) and rs7501331 in the gene BCMO1 (P = 0.0106, OR = 0.24, 95% C.I.:0.21-0.71), are significantly associated (the latter marginally significant) with the decrease of the risk of the disease. Also for this SNPs there were significant differences in the genotypic frequencies in the study population. There was a link between rs12934922 of BCMO1 gen and serum concentration of RBP4 (P = 0.034) and adiponectin (P = 0.038) in the study group but not in the control group. The elevated mean serum concentration of cholesterol (P = 0.020) and LDL cholesterol (P = 0.005) was observed for GG rs1501299 genotype and triglycerides (P = 0.028) for TT rs2241766 genotype.
CONCLUSIONS: The results of the present study revealed that the genes variants RBP4 is not associated with PCO. It seems that rs1501299 of ADIPOQ gene influences the occurrence of PCO and lipids profile in those patients.

Sinreih M, Knific T, Thomas P, et al.
Membrane progesterone receptors β and γ have potential as prognostic biomarkers of endometrial cancer.
J Steroid Biochem Mol Biol. 2018; 178:303-311 [PubMed] Related Publications
Endometrial cancer (EC) is one of the most common malignancies in women worldwide. EC is linked to chronic exposure to estrogens that is unopposed by protective effects of progesterone. Progesterone modulates gene expression via classical nuclear receptors, and has rapid effects via the less characterized membrane-bound progesterone receptors (mPRs) of the progestin and adipoQ receptor (PAQR) family. The presence of mPRs in EC has not been investigated to date. The aims of this study were to examine PAQR7, PAQR8 and PAQR5, which encode for mPRα, mPRβ and mPRγ, respectively, for their expression and localization in EC tissue and adjacent control endometrium. Our results reveal decreased expression of PAQR7 and PAQR8, and unaltered expression of PAQR5 in EC versus control tissue. Expression of PAQR5 was decreased in EC with higher FIGO stage versus stage IA. Immunohistochemistry revealed lower levels of mPRα and mPRβ, but higher levels of mPRγ, in EC versus control tissue. There was greater decrease in mPRβ levels in tumors with lymphovascular invasion. The analysis of the expression data associates higher PAQR5 mRNA and mPRβ protein levels with favorable patient prognosis. Immunohistochemistry showed diverse localizations of mPRs in control and cancer endometrium. In control endometrium, mPRα and mPRβ were localized mostly at the cell membranes, while mPRγ was localized in the cytoplasm and/or nucleus. In cancer endometrium, mPRα and mPRβ were detected at the cell membrane or in the cytoplasm, or both, while mPRγ was only localized in the cytoplasm. Taken together, these results imply that mPRs are involved in EC pathogenesis through effects on the development or progression of cancer. The potential role of mPRβ and mPRγ as prognostic biomarkers needs to be further assessed on a larger number of samples.

Harada H, Tsuda Y, Yabuki K, et al.
Inhibition of WNT/β-catenin signaling under serum starvation and hypoxia induces adipocytic transdifferentiation in human leiomyoma cells.
Lab Invest. 2018; 98(4):439-448 [PubMed] Related Publications
Fatty metamorphosis is an uncommon alteration in uterine leiomyoma (i.e., lipoleiomyoma), and the pathogenetic mechanisms underlying this phenomenon remain poorly understood. Because a conditional deletion of β-catenin, a major transducer of the canonical Wingless/integrated (WNT) pathway, in the developing mouse uterus can induce adipogenesis in the myometrium, it is hypothesized that inhibition of the WNT/β-catenin signaling may be also involved in the development of fat cells within uterine leiomyoma. In the current study, which was performed to address this point, intracytoplasmic lipid droplets were detectable in cultured human leiomyoma cells by treatment with a potent tankyrase inhibitor, XAV939, which antagonizes β-catenin, in a serum-starved culture medium without additional adipogenesis-inducing agents or supplements, and showed increasing accumulation in a time-dependent manner. In addition, the induction of fat cells was greatly enhanced under hypoxic conditions (i.e., 2.5% O

Busch EL, Crous-Bou M, Prescott J, et al.
Adiponectin, Leptin, and Insulin-Pathway Receptors as Endometrial Cancer Subtyping Markers.
Horm Cancer. 2018; 9(1):33-39 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Developing a system of molecular subtyping for endometrial tumors might improve insight into disease etiology and clinical prediction of patient outcomes. High body mass index (BMI) has been implicated in development of endometrial cancer through hormonal pathways and might influence tumor expression of biomarkers involved in BMI-sensitive pathways. We evaluated whether endometrial tumor expression of 7 markers from BMI-sensitive pathways of insulin resistance could effectively characterize molecular subtypes: adiponectin receptor 1, adiponectin receptor 2, leptin receptor, insulin receptor (beta subunit), insulin receptor substrate 1, insulin-like growth factor 1 receptor, and insulin-like growth factor 2 receptor. Using endometrial carcinoma tissue specimens from a case-only prospective sample of 360 women from the Nurses' Health Study, we scored categorical immunohistochemical measurements of protein expression for each marker. Logistic regression was used to estimate associations between endometrial cancer risk factors, especially BMI, and tumor marker expression. Proportional hazard modeling was performed to estimate associations between marker expression and time to all-cause mortality as well as time to endometrial cancer-specific mortality. No association was observed between BMI and tumor expression of any marker. No marker was associated with time to either all-cause mortality or endometrial cancer-specific mortality in models with or without standard clinical predictors of patient mortality (tumor stage, grade, and histologic type). It did not appear that any of the markers evaluated here could be used effectively to define molecular subtypes of endometrial cancer.

Echiburú B, Pérez-Bravo F, Galgani JE, et al.
Enlarged adipocytes in subcutaneous adipose tissue associated to hyperandrogenism and visceral adipose tissue volume in women with polycystic ovary syndrome.
Steroids. 2018; 130:15-21 [PubMed] Related Publications
CONTEXT: Polycystic ovary syndrome (PCOS) is an androgen excess disorder associated with obesity and adipose tissue disturbances. Our aim was to evaluate gene expression of adipocytokines and adipocyte characteristics in abdominal subcutaneous adipose tissue (SAT) of PCOS women.
DESIGN: Twelve PCOS (PCOSw) and 12 control (Cw) premenopausal women (BMI 20-35 kg/m
RESULTS: Both groups were comparable in age and BMI. Trunk fat mass amount (p = .043), serum and SAT leptin/adiponectin ratio (p = .034 and p = .028, respectively) and adipocyte area (p = .015) were higher in PCOSw compared to Cw. Interestingly, trunk fat mass was positively correlated with adipocyte area in PCOSw (r = 0.821, p = .023), while the inverse correlation was found in Cw (r = -0.786, p = .021). Only in PCOSw, adipocyte area was positively correlated with serum testosterone (r = 0.857, p = .014) and visceral adipose tissue volume (r = 0.857, p = .014).
CONCLUSIONS: Our results indicate that PCOS women present adipose tissue dysfunction in the subcutaneous compartment, characterized by an alteration in adipocyte size and leptin/adiponectin expression and secretion, probably associated with higher androgen concentrations.

Chen Z, Yu R, Xiong Y, et al.
A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease.
Lipids Health Dis. 2017; 16(1):203 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of diseases, including simple steatosis, nonalcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma. Lipotoxicity, insulin resistance (IR) and inflammation are involved in the disease process. Lipotoxicity promotes inflammation and IR, which in turn, increase adipocyte lipolysis and exacerbates lipotoxicity. Furthermore, IR and inflammation form a vicious circle, with each condition promoting the other and accelerating the development of NAFLD in the presence of lipotoxicity. As an integrator of inflammatory pathway networks, nuclear factor-kappa B (NF-κB) regulates expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and anti-inflammatory cytokines, such as adiponectin in NAFLD. In this review, the relationships between lipotoxicity, IR and inflammation in NAFLD are discussed, with particular emphasis on the inflammatory pathways.

Wang L, Zhang R, You X, et al.
The steady-state level of CDK4 protein is regulated by antagonistic actions between PAQR4 and SKP2 and involved in tumorigenesis.
J Mol Cell Biol. 2017; 9(5):409-421 [PubMed] Related Publications
CDK4 is crucial for G1-to-S transition of cell cycle. It is well established that ubiquitin-mediated degradations of CDK inhibitors and cyclins are pivotal for the timely and unidirectional progression of cell cycle. However, how CDK4 itself is modulated by ubiquitin-mediated degradation has been elusive. Here we report that the steady-state level of CDK4 is controlled by PAQR4, a member of the progestin and adipoQ receptor family, and SKP2, an E3 ubiquitin ligase. Knockdown of PAQR4 leads to reduction of cell proliferation, accompanied by reduced protein level of CDK4. PAQR4 reduces polyubiquitination and degradation of CDK4. PAQR4 interacts with the C-terminal lobe of CDK4. On the other hand, SKP2 also interacts with the C-terminal lobe of CDK4 and enhances polyubiquitination and degradation of CDK4. Importantly, PAQR4 and SKP2 bind to the same region in CDK4, and PAQR4 competes with SKP2 for the binding, thereby abrogating SKP2-mediated ubiquitination of CDK4. Using a two-stage DMBA/TPA-induced skin cancer model, we find that PAQR4-deleted mice are resistant to chemical carcinogen-induced tumor formation. Collectively, our findings reveal that the steady-state level of CDK4 is controlled by the antagonistic actions between PAQR4 and SKP2, contributing to modulation of cell proliferation and tumorigenesis.

Bai G, Chu J, Eli M, et al.
PAQR3 overexpression suppresses the aggressive phenotype of esophageal squamous cell carcinoma cells via inhibition of ERK signaling.
Biomed Pharmacother. 2017; 94:813-819 [PubMed] Related Publications
Progestin and adipoQ receptor family member 3 (PAQR3) has exhibited anticancer activity in multiple malignancies. However, its expression and function in esophageal squamous cell carcinoma (ESCC) is still elusive. In this work, we examined the expression of PAQR3 in 40 surgically resected ESCC specimens and their adjacent normal tissues. The expression of PAQR3 in ESCC cell lines was measured after treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-Aza-CdR). The effects of overexpression of PAQR3 on cell proliferation, colony formation, invasion, and tumorigenesis were investigated. It was found that the PAQR3 mRNA level was significantly lower in ESCC than that in adjacent normal tissues (P=0.0318). Low PAQR3 expression was significantly associated with more advanced TNM stage (P=0.0093) and absent lymph node involvement (P=0.0324). Compared to normal esophageal epithelial cells, ESCC cells had significantly lower levels of PAQR3. 5-Aza-CdR treatment led to an induction of PAQR3 in ESCC cells. Enforced expression of PAQR3 significantly inhibited ESCC cell proliferation, colony formation and invasion. Moreover, PAQR3 overexpression blocked cell cycle transition from G1 to S phase, which was associated with induction of p27 and p21 and reduction of cyclin D1, CDK4, and CDK2. Mechanistically, overexpression of PAQR3 suppressed the phosphorylation of ERK1/2 in ESCC cells. In vivo tumorigenic studies confirmed that PAQR3 overexpression retarded the growth of ECA-109 xenograft tumors and inhibited the activation of ERK signaling. Taken together, PAQR3 is epigenetically silenced in ESCC and restoration of PAQR3 suppresses the aggressive phenotype of ESCC cells. Therefore, PAQR3 may represent a potential target for the treatment of ESCC.

Zhao C, Li Y, Chen G, et al.
Overexpression of miR-15b-5p promotes gastric cancer metastasis by regulating PAQR3.
Oncol Rep. 2017; 38(1):352-358 [PubMed] Related Publications
Gastric cancer (GC) is the fifth most common cancer in the world, with 952,000 new cases diagnosed in 2012. Tumor metastasis is the major cause of cancer recurrence and death. miR-15b-5p has been reported to be dysregulated in numerous types of cancers. However, the role of miR-15b-5p in GC metastasis remains unclear. An miRNA microarray was adopted to analyze the miRNA expression profile. By employing quantitative real-time polymerase chain reaction (qRT-PCR), miR-15b-5p expression levels were detected in GC cell lines, tissues and plasma samples. In addition, the effects of miR-15b-5p on cell proliferation, migration and invasion were studied by applying gain-of-function approaches. Moreover, the target of miR-15b-5p was assessed by dual-luciferase assay, and the mechanism underlying the regulation of GC metastasis by miR-15b-5p was assessed by rescue experiments. The results revealed that miR-15b-5p was upregulated in GC cell lines, tissues and plasma samples. A high plasma level of miR-15b-5p was correlated with distant tumor metastasis. In addition, overexpression of miR‑15b-5p in GC cells promoted cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Moreover, progestin and adipoQ receptor family member 3 (PAQR3) was found to be a direct target of miR-15b-5p and re-expression of PAQR3 in miR-15b-5p-overexpressing GC cells partly attenuated the proliferation, migration and invasion. These findings revealed that miR-15b-5p promotes the metastasis of GC cells through PAQR3 and may represent a potential biomarker of GC.

Nimptsch K, Song M, Aleksandrova K, et al.
Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies.
Eur J Epidemiol. 2017; 32(5):419-430 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.

Zhou F, Wang S, Wang J
PAQR3 Inhibits the Proliferation and Tumorigenesis in Esophageal Cancer Cells.
Oncol Res. 2017; 25(5):663-671 [PubMed] Related Publications
Progestin and adipoQ receptor family member III (PAQR3), a member of the PAQR family, is frequently downregulated in different types of human cancer. However, its expression and functions in esophageal cancer are still unknown. This study aimed to explore the expression of PAQR3 in esophageal cancer cell lines and to investigate the role of PAQR3 in the development of esophageal cancer. Our data showed that PAQR3 is expressed in low amounts in human esophageal cancer cell lines. Overexpression of PAQR3 significantly suppressed the proliferation, migration, and invasion of esophageal cancer cells. In addition, overexpression of PAQR3 downregulated the protein expression levels of RAF1, p-MEK1, and p-ERK1/2 in esophageal cancer cells. Furthermore, overexpression of PAQR3 attenuated the tumor growth in a tumor xenograft model. In conclusion, we demonstrated that overexpression of PAQR3 suppresses cell proliferation, migration, and invasion in esophageal cancer in vitro and in vivo. Therefore, PAQR3 may act as a therapeutic target for human esophageal cancer.

Canto P, Granados JB, Feria-Bernal G, et al.
PPARGC1A and ADIPOQ polymorphisms are associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity.
Cancer Biomark. 2017; 19(3):297-303 [PubMed] Related Publications
BACKGROUND: Obesity constitutes a risk factor for the development of aggressive forms of prostate cancer. It has been proposed, that prostate cancer has a genetic predisposition and that PPARGC1A and ADIPOQ polymorphisms play a role in the development of this condition.
OBJECTIVE: To analyse the association of two PPARGC1A and ADIPOQ polymorphisms as well as their haplotypes, with the development of aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity.
SUBJECTS AND METHODS: Two hundred fifty seven men with prostate cancer of Mexican-Mestizo origin were included. Body mass index (BMI) was determined and the degree of prostate cancer aggressiveness by the D'Amico classification. DNA was obtained. Rs7665116 and rs2970870 of PPARGC1A, and rs266729 and rs1501299 of ADIPOQ were studied by real-time PCR allelic discrimination. Pairwise linkage disequilibrium, between single nucleotide polymorphisms was calculated and haplotype analysis was performed.
RESULTS: A higher-risk (D'Amico classification) was observed in 21.8% of patients. An association of cancer aggressiveness with rs2970870 of PPARGC1A, and rs501299 of ADIPOQ, as well as with one haplotype of ADIPOQ was documented.
CONCLUSIONS: This is the first study regarding the relationship of PPARGC1A and ADIPOQ polymorphisms, and the aggressiveness of prostate cancer in men with overweight or obesity.

Méndez-Hernández A, Gallegos-Arreola MP, Moreno-Macías H, et al.
LEP rs7799039, LEPR rs1137101, and ADIPOQ rs2241766 and 1501299 Polymorphisms Are Associated With Obesity and Chemotherapy Response in Mexican Women With Breast Cancer.
Clin Breast Cancer. 2017; 17(6):453-462 [PubMed] Related Publications
BACKGROUND: Obesity plays a major role in the pathogenesis of breast cancer. Leptin (LEP) and adiponectin (ADIPOQ) are important in the regulation of adipose tissue. The response to cancer treatment depends on the histological and molecular tumor type, clinical stage, and genetic variability that might promote carcinogenic development. The aim of this study was to investigate the association between overweight/obesity and polymorphisms in the LEP (rs7799039), LEP receptor (LEPR; rs1137101), and ADIPOQ genes (rs2241766, rs1501299) with the response to breast cancer treatment in Mexican women.
PATIENTS AND METHODS: A sample of 177 patients with primary breast cancer (stage I-III) and who received neoadjuvant therapy were included. Polymorphisms were genotyped and their serum LEP concentrations (n = 59) were quantified.
RESULTS: The patients' median age was 53.1 years, the frequency of overweight and obesity was 57 and 84 patients, respectively, 117 were postmenopausal, and 64 of the patients did not respond to chemotherapy. An association of the LEP rs7799039, LEPR rs1137101, and ADIPOQ rs1501299 polymorphisms with overweight/obesity was found. The patients who did not respond to treatment were more frequently obese, at clinical stage III, had metastases, and high levels of glucose. Moreover, in samples that were positive for estrogen receptor, higher levels of LEP were found, and in wild type genotypes for LEP rs7799039 and LEPR rs1137101.
CONCLUSION: There was a direct association between the polymorphisms in LEP rs7799039 and ADIPOQ rs1501299 with overweight/obesity, and these genotypes affected the response to chemotherapeutic treatment, suggesting that an obesogenic microenvironment is more favorable for tumoral progression.

Tan X, Wang GB, Tang Y, et al.
Association of ADIPOQ and ADIPOR variants with risk of colorectal cancer: A meta-analysis.
J Huazhong Univ Sci Technolog Med Sci. 2017; 37(2):161-171 [PubMed] Related Publications
Numerous epidemiological studies have studied the association of adiponectin (ADIPOQ) gene and adiponectin receptor (ADIPOR) gene polymorphisms with risk of colorectal cancer (CRC), but the outcomes were incomplete and inconsistent. Therefore, we conducted a meta-analysis to assess the associations systematically. All eligible case-control studies published up to Jan. 2015 were searched from PubMed, the Cochrane library, Elsevier, Wiley Online library, China National Knowledge Infrastructure, WanFang data and Chongqing VIP. Effect sizes of odds ratio (OR) and 95% confidence interval (95%CI) were calculated by using a fixed- or random-effect model. Twelve case-control studies including 6141 cases and 7398 controls were selected. Significant differences in the distributions of allele frequency with CRC risk were directly present in ADIPOQ variants rs2241766, rs1501299 and ADIPOR variant rs1342387. In stratified analysis for different populations, significant differences were present in ADIPOQ variant rs822396 for Ashkenazi Jewish, in ADIPOQ variant rs1501299 and ADIPOR variant rs1342387 for Chinese and in ADIPOQ variant rs 2241766 for Ashkenazi Jewish and Chinese. In addition, the factors correlated with insulin resistance had synergistic effect with ADIPOQ variants rs2241766 T/G and rs1501299 G/T on risk of CRC. ADIPOQ variants rs2241766 T/G, rs1501299 G/T and ADIPOR variant ADIPOR rs1342387 G/A had a population specific correlation with CRC risk, which may be mediated by insulin resistance. And large well-designed studies are still needed for further evaluation of rs822396 and rs1063538, especially for their interaction and combined effect in the correlation with CRC risk.

Brown KA, Iyengar NM, Zhou XK, et al.
Menopause Is a Determinant of Breast Aromatase Expression and Its Associations With BMI, Inflammation, and Systemic Markers.
J Clin Endocrinol Metab. 2017; 102(5):1692-1701 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Context: Most estrogen-dependent breast cancers occur after menopause, despite low levels of circulating estrogens. Breast expression of the estrogen-biosynthetic enzyme, aromatase, is proposed to drive breast cancer development after menopause. However, the effects of menopause on breast aromatase expression are unknown.
Objective: To determine the effect of menopause on breast aromatase expression in relation to body mass index (BMI), white adipose tissue inflammation (WATi), and systemic markers of metabolic dysfunction.
Design, Setting, and Participants: Cross-sectional study of 102 premenopausal (age 27 to 56) and 59 postmenopausal (age 45 to 74) women who underwent mastectomy for breast cancer treatment/prevention.
Outcome: Breast tissue was assessed for the presence of crown-like structures and the expression and activity of aromatase. Systemic markers examined include interleukin (IL)-6, insulin, glucose, leptin, adiponectin, high-sensitivity C-reactive protein (hsCRP), cholesterol, and triglycerides. Multivariable analysis was performed for aromatase messenger RNA (mRNA) in relation to BMI, WATi, and blood markers.
Results: Postmenopausal women had higher BMI and more breast WATi than premenopausal women. Fasting levels of IL-6, glucose, leptin, hsCRP, and homeostatic model assessment 2 insulin resistance score were higher in the postmenopausal group. BMI was positively correlated with aromatase mRNA in both pre- and postmenopausal women. Aromatase levels were higher in breast tissue of postmenopausal women, with levels being higher in inflamed vs noninflamed, independent of BMI. Adipocyte diameter and levels of leptin, hsCRP, adiponectin, and high-density lipoprotein cholesterol were more strongly correlated with aromatase in postmenopausal than premenopausal women.
Conclusions: Elevated aromatase in the setting of adipose dysfunction provides a possible mechanism for the higher incidence of hormone-dependent breast cancer in obese women after menopause.

Sadim M, Xu Y, Selig K, et al.
A prospective evaluation of clinical and genetic predictors of weight changes in breast cancer survivors.
Cancer. 2017; 123(13):2413-2421 [PubMed] Related Publications
BACKGROUND: Postdiagnosis weight gain in patients with breast cancer has been associated with increased cancer recurrence and mortality. This study was designed to identify risk factors for weight gain and create a predictive model to identify a high-risk population for targeted interventions.
METHODS: The weight of 393 patients with breast cancer from the Northwestern Robert H. Lurie Cancer Center was measured over a 2-year period from diagnosis, with body mass index (BMI) change over 18 months as the primary endpoint. Demographics, clinical factors, treatment methods, as well as tumor characteristics were also recorded; and a lifestyle questionnaire was conducted. Blood samples were genotyped for 16 single nucleotide polymorphisms in FTO, adiponectin pathway genes (ADIPOQ, ADIPOR1), and FNDC5. Serum leptin, adiponectin, and irisin levels also were measured.
RESULTS: Mean ± standard deviation 18-month BMI changes were 0.68 ± 1.42, 0.98 ± 1.62, 0.79 ± 1.74, and -0.44 ± 1.58 kg/m
CONCLUSIONS: Women age 60 years and younger at the time of breast cancer diagnosis who have an obesity genetic risk model are at increased risk for weight gain after treatment and should be targeted for weight-maintenance interventions. Cancer 2017;123:2413-21. © 2017 American Cancer Society.

Sun X, Wu X, Duan Y, et al.
Family-Based Association Study of rs17300539 and rs12495941 Polymorphism in Adiponectin Gene and Polycystic Ovary Syndrome in a Chinese Population.
Med Sci Monit. 2017; 23:78-84 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
BACKGROUND Polycystic ovary syndrome (PCOS) is a complex disease that has both genetic and environmental components. Adiponectin plays an important role in the regulation of insulin sensitivity and insulin resistance (IR) in PCOS. The aim of this study was to determine 2 single-nucleotide polymorphisms (SNPs) variants (rs12495941 and rs17300539) of the adiponectin gene (ADIPOQ) in polycystic ovary syndrome (PCOS) families. MATERIAL AND METHODS We recruited 197 PCOS probands, their biological parents, and 192 controls. Anthropometric variables, including hip circumference (HC) and waist circumference (WC), were measured in all subjects during their first visit to the outpatient department. Serum T, FBG, FINS, TC, TG, LDL, and HDL levels were measured. PCOS patients were divided into 2 groups based on BMI: group A (BMI <25 kg/m²) and group B (BMI ≥25 kg/m²). Parents of PCOS were accordingly categorized into group C and group D (fathers), and group E and group F (mothers). The associations among ADIPOQ rs12495941, rs17300539, and PCOS were analyzed using the transmission disequilibrium test (TDT). RESULTS A significant association was found between SNP rs17300539 and PCOS in our Chinese population. The levels of TG and FINS and the genotype frequencies of rs17300539 are significantly different between overweight and lean PCOS. No significant association was detected for rs12495941. CONCLUSIONS TDT confirms that rs17300539 of ADIPOQ is strongly associated with the risk of PCOS in a Chinese Han population, but rs12495941 of ADIPOQ is not associated with the occurrence of PCOS.

Makoukji J, Makhoul NJ, Khalil M, et al.
Gene expression profiling of breast cancer in Lebanese women.
Sci Rep. 2016; 6:36639 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Breast cancer is commonest cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. Molecular alterations in breast cancer are complex and involve cross-talk between multiple signaling pathways. The aim of this study is to extract a unique mRNA fingerprint of breast cancer in Lebanese women using microarray technologies. Gene-expression profiles of 94 fresh breast tissue samples (84 cancerous/10 non-tumor adjacent samples) were analyzed using GeneChip Human Genome U133 Plus 2.0 arrays. Quantitative real-time PCR was employed to validate candidate genes. Differentially expressed genes between breast cancer and non-tumor tissues were screened. Significant differences in gene expression were established for COL11A1/COL10A1/MMP1/COL6A6/DLK1/S100P/CXCL11/SOX11/LEP/ADIPOQ/OXTR/FOSL1/ACSBG1 and C21orf37. Pathways/diseases representing these genes were retrieved and linked using PANTHER

Ye L, Wang G, Tang Y, Bai J
A population-specific correlation between ADIPOQ rs2241766 and rs 1501299 and colorectal cancer risk: a meta-analysis for debate.
Int J Clin Oncol. 2017; 22(2):307-315 [PubMed] Related Publications
AIMS: Many epidemiological studies have investigated the correlation between adiponectin, C1Q and collagen domain containing (ADIPOQ) single nucleotide polymorphisms (SNPs) and risk of colorectal cancer (CRC). Although conflicting results have been reported, there was dispute regarding two SNPs (rs2241766 T/G and rs1501299 G/T). Therefore, we conducted a meta-analysis to systematically assess the associations and try to find the reasons for the dispute.
METHODS: We searched PubMed, the Cochrane Library, Elsevier, Wiley Online Library, China National Knowledge Infrastructure, WanFang data and Chongqing VIP to search for all eligible case-control studies published up to January 2015. Effect sizes of odds ratios (OR) and 95 % confidence intervals (95 % CI) were calculated using a fixed- or random-effect model.
RESULTS: Ten case-control studies including 4377 cases and 5584 controls were selected. A significant difference was observed in Chinese (OR 0.76; 95 % CI 0.68, 0.85; P < 0.001) and Ashkenazi Jewish populations (OR 0.79; 95 % CI 0.63, 0.99; P = 0.04) for rs2241766 with dominant model (TT vs TG + GG). A significant difference was observed in the Chinese population (OR 1.23; 95 % CI 1.11, 1.37; P < 0.001) for rs1501299 with dominant model (TT vs TG + GG). In addition, intake of red meat showed a synergistic effect between ADIPOQ gene and risk of colorectal cancer (CRC).
CONCLUSIONS: ADIPOQ SNPs rs2241766 T/G and rs 1501299 G/T have a population-specific correlation with risk of CRC. However, small sample studies may increase reporting bias, particularly if the total number of studies included in the analysis is small.

Chan AW, Wong GL, Chan HY, et al.
Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B.
J Gastroenterol Hepatol. 2017; 32(3):667-676 [PubMed] Related Publications
BACKGROUND AND AIMS: Concurrent fatty liver in hepatitis B virus (HBV)-infected patients without significant alcohol intake is a frequent and increasingly alarming problem because of the non-alcoholic fatty liver disease pandemic. The risk of HBV-related hepatocellular carcinoma (HCC) development was increased by concomitant obesity and diabetes. Direct evidence of the hepatocarcinogenic effect of fatty liver in chronic HBV remains elusive. We aimed to evaluate the risk of concurrent histologically proven fatty liver in HBV hepatocarcinogenesis.
METHODS: We conducted a retrospective cohort study on a liver biopsy cohort of HBV-infected patients without significant alcohol intake to evaluate the prevalence of concurrent histologically proven fatty liver and its association with subsequent HCC development. We also examined nine polymorphisms on six non-alcoholic fatty liver disease-related candidate genes (ADIPOQ, APOC3, GCKR, LEPR, PNPLA3, and PPARG).
RESULTS: Among 270 HBV-infected patients, concurrent fatty liver was found in 107 patients (39.6%) and was associated with metabolic risks, cirrhosis (P = 0.016) and PNPLA3 rs738409 CG/GG genotype (P = 0.002). At a median follow-up of 79.9 months, 11 patients (4.1%) developed HCC, and nine of them had concurrent fatty liver. By multivariable Cox analysis, concurrent fatty liver (HR 7.27, 95% confidence interval: 1.52-34.76; P = 0.013), age, cirrhosis, and APOC3 rs2854116 TC/CC genotype (HR 3.93, 95% confidence interval: 1.30-11.84; P = 0.013) were independent factors predicting HCC development.
CONCLUSIONS: Concurrent fatty liver is common in HBV-infected patients and an independent risk factor potentiating HBV-associated HCC development by 7.3-fold. The risk of HBV-related HCC is increased by APOC3 gene polymorphism, and further characterization is required by its role.

Goncharov AI, Maslakova AA, Polikarpova AV, et al.
Progesterone inhibits proliferation and modulates expression of proliferation-Related genes in classical progesterone receptor-negative human BxPC3 pancreatic adenocarcinoma cells.
J Steroid Biochem Mol Biol. 2017; 165(Pt B):293-304 [PubMed] Related Publications
Recent studies suggest that progesterone may possess anti-tumorigenic properties. However, a growth-modulatory role of progestins in human cancer cells remains obscure. With the discovery of a new class of membrane progesterone receptors (mPRs) belonging to the progestin and adipoQ receptor gene family, it becomes important to study the effect of this hormone on proliferation of tumor cells that do not express classical nuclear progesterone receptors (nPRs). To identify a cell line expressing high levels of mPRs and lacking nPRs, we examined mRNA levels of nPRs and three forms of mPRs in sixteen human tumor cell lines of different origin. High expression of mPR mRNA has been found in pancreatic adenocarcinoma BxPC3 cells, while nPR mRNA has not been detected in these cells. Western blot analysis confirmed these findings at the protein level. We revealed specific binding of labeled progesterone in these cells with affinity constant similar to that of human mPR expressed in yeast cells. Progesterone at high concentration of 20 μM significantly reduced the mRNA levels of proliferation markers Ki67 and PCNA, as well as of cyclin D1, and increased the mRNA levels of cyclin dependent kinase inhibitors p21 and p27. Progesterone (1 μM and 20 μM) significantly inhibited proliferative activity of BxPC3 cells. These results point to anti-proliferative effects of the progesterone high concentrations on BxPC3 cells and suggest that activation of mPRs may mediate this action. Our data are a starting point for further investigations regarding the application of progesterone in pancreatic cancer.

Hlavaty J, Ertl R, Miller I, Gabriel C
Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro.
Biomed Res Int. 2016; 2016:8065830 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Objective. Some effects of progesterone on glioma cells can be explained through the slow, genomic mediated response via nuclear receptors; the other effects suggest potential role of a fast, nongenomic action mediated by membrane-associated progesterone receptors. Methods. The effects of progesterone treatment on the expression levels of progesterone receptor membrane component 1 (PGRMC1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1), and progestin and adipoQ receptor 7 (PAQR7) on both mRNA and protein levels were investigated in spheroids derived from human glioma cell lines U-87 MG and LN-229. Results. The only significant alteration at the transcript level was the decrease in PGRMC1 mRNA observed in LN-229 spheroids treated with 30 ng/mL of progesterone. No visible alterations at the protein levels were observed using immunohistochemical analysis. Stimulation of U-87 MG spheroids resulted in an increase of PGRMC1 but a decrease of PAIRBP1 protein. Double immunofluorescent detection of PGRMC1 and PAIRBP1 identified the two proteins to be partially colocalized in the cells. Western blot analysis revealed the expected bands for PGRMC1 and PAIRBP1, whereas two bands were detected for PAQR7. Conclusion. The progesterone action is supposed to be mediated via membrane-associated progesterone receptors as the nuclear progesterone receptor was absent in tested spheroids.

Dehghan R, Saidijam M, Mehdizadeh, et al.
Evidence for decreased expression of APPL1 associated with reduced insulin and adiponectin receptors expression in PCOS patients.
J Endocrinol Invest. 2016; 39(9):1075-82 [PubMed] Related Publications
PURPOSE: To investigate the expression of Adaptor protein containing a PH domain, PTB domain and leucine zipper motif 1 (APPL1), insulin receptor (INSR), adiponectin and adiponectin receptors (adipoR1 and R2) and their possible associations in granulosa cells (GCs) of 22 polycystic ovary syndrome (PCOS) women compared to the 22 non-PCOS controls with normal ovulatory function matched for BMI (body mass index).
METHODS: In this study, 44 infertile women aged 18-40 years undergoing in vitro fertilization (IVF) protocol were recruited. After follicular fluid collection, GCs were isolated and then purified with MACS (Micro Beads conjugated to monoclonal anti-human CD45 antibodies). RNA was extracted from GCs and quantitative real-time PCR (qRT-PCR) was performed to assess APPL1 gene expression.
RESULTS: Expression of APPL1, insulin receptor and adiponectin system genes was significantly decreased in PCOS group compared to the controls.
CONCLUSIONS: Reduction of APPL1, insulin receptor and adiponectin system genes in GCs could be involved in the development of PCOS.

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