Association of SNPs in miR-146a, miR-196a2, and miR-499 with the risk of endometrial/ovarian cancer

Liu, Xiaoyan; Xu, Beihui; Li, Shujin; Zhang, Bin; Mao, Peimin; Qian, Beibei; Guo, Lin; Ni, Peihong

doi:10.1093/abbs/gmv042

Cited by 21 publications

(17 citation statements)

References 9 publications

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“…We report for the first time that increased expression of miR146-a, a microRNA that has been experimentally shown to bind and degrade THRB mRNA in papillary thyroid carcinoma [35], is associated with the loss of THRB expression in endometrial carcinomas. In addition, a previous study found a single nucleotide polymorphism (rs2910164 G > C) within the pre-miRNA of miR146-a that decreases the risk for endometrial and ovarian cancer [41]. However, further studies are warranted to conclusively determine the relationship between miR146-a and THRB expression in endometrial cancer.…”

Section: Discussionmentioning

confidence: 97%

Identification of a novel subgroup of endometrial cancer patients with loss of thyroid hormone receptor beta expression and improved survival

2020

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Background Endometrial cancer (EC) is the most common gynecologic cancer in women, and the incidence of EC has increased by about 1% per year in the U. S over the last 10 years. Although 5-year survival rates for early-stage EC are around 80%, certain subtypes of EC that lose nuclear hormone receptor (NHR) expression are associated with poor survival rates. For example, estrogen receptor (ER)-negative EC typically harbors a worse prognosis compared to ER-positive EC. The molecular basis for the loss of NHR expression in endometrial tumors and its contribution to poor survival is largely unknown. Furthermore, there are no tools to systematically identify tumors that lose NHR mRNA expression relative to normal tissue. The development of such an approach could identify sets of NHR-based biomarkers for classifying patients into subgroups with poor survival outcomes. Methods Here, a new computational method, termed receptLoss, was developed for identifying NHR expression loss in endometrial cancer relative to adjacent normal tissue. When applied to gene expression data from The Cancer Genome Atlas (TCGA), receptLoss identified 6 NHRs that were highly expressed in normal tissue and exhibited expression loss in a subset of endometrial tumors. Results Three of the six identified NHRs – estrogen, progesterone, and androgen receptors – that are known to lose expression in ECs were correctly identified by receptLoss. Additionally, a novel association was found between thyroid hormone receptor beta (THRB) expression loss, increased expression of miRNA-146a, and increased rates of 5-year survival in the EC TCGA patient cohort. THRB expression loss occurs independently of estrogen and progesterone expression loss, suggesting the discovery of a distinct, clinically-relevant molecular subgroup. Conclusion ReceptLoss is a novel, open-source software tool to systematically identify NHR expression loss in cancer. The application of receptLoss to endometrial cancer gene expression data identified THRB, a previously undescribed biomarker of survival in endometrial cancer. Applying receptLoss to expression data from additional cancer types could lead to the development of biomarkers of disease progression for patients with any other tumor type. ReceptLoss can be applied to expression data from additional cancer types with the goal of identifying biomarkers of differential survival.

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Section: Discussionmentioning

confidence: 97%

Identification of a novel subgroup of endometrial cancer patients with loss of thyroid hormone receptor beta expression and improved survival

2020

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“…High expression of miRNAs causing abnormal proliferation and migration of tumor cells can induce cancer, however in other cases the role of miRNAs can be tumor suppression ( 13 ). In studies of miRNAs, it has been observed that miR-146a expression is significantly higher in a variety of tumor cells than in normal tissues, and miR-146a is mostly involved in inflammation ( 14 – 16 ). A study found that breast cancer cells expressing high levels of miR-146a were more prone to distant metastasis than tumor cells with low expression levels of miR-146a ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

miR-146a and miR-146b in the diagnosis and prognosis of papillary thyroid carcinoma

Qiu

Wang

et al. 2017

Oncology Reports

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The present study investigated the relationship between the expression of miR-146a and miR-146b with the occurrence and prognosis of papillary thyroid carcinoma. Experiments in vitro were also used to explore the effect of the knocked down expression of the miRNAs on growth and migration of papillary thyroid carcinoma cells. A total of 73 patients with papillary thyroid carcinoma admitted to Yidu Central Hospital of Weifang from September 2013 to September 2015 were enrolled in the study. Carcinoma samples were obtained from each patient, and adjacent tissues were used as control samples to determine expression levels of miR-146a and miR146b by semi-quantitative RT-PCR. An analysis was conducted to find possible correlations between the miRNAs expression levels and clinicopathological features in the patients followed up for one year after diagnosis. Additionally, to examine the function of miR-146a and miR-146b on TPC-1 cells, the expression of miRNAs was knocked down using specific siRNAs. MTT and Transwell assays were used to evaluate cell proliferation and migration, respectively, in the miRNA cell lines. Finally, western blot analysis was used to analyze the expression of IRAK1 in PTC cancer cells. Our results showed that the expression levels of miR-146a and miR-146b in carcinoma tissues were significantly higher than the levels in cancer-free tissues (P<0.01). The relative expression levels of miR-146a and miR-146b in cancerous tissues could be associated with the pathological type and presence or absence of lymph node metastasis (P<0.05). Compared with the siRNA-control cell, MTT and Transwell assays showed that the cell growth and migration of TPC-1 cells were decreased in miR-146a and miR-146b low expression cells (P<0.01). Western blot analysis showed that the expression of IRAK1 in papillary thyroid carcinoma was higher than in adjacent tissue (P<0.01). Based on our findings, the expression of miR-146a and miR-146b correlates with the occurrence and prognosis of papillary thyroid carcinoma, and the expression levels of miR-146a and miR-146b seem to affect the cell proliferation and migration and regulate the expression of IRAK1 protein in cancer cells. Further studies are needed to validate our results to provide new targets for prevention and treatment of papillary thyroid carcinoma.

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“…Currently, only three studies analyzed the association between the miR-146a polymorphism and ovarian cancer in a Caucasian population (Shen et al, 2008;Pastrello et al, 2010;Liu et al, 2015). The C allele variant of miR-146a was associated with early familial breast and ovarian tumor development in a study conducted on 101 Italian patients with ovarian cancer and 155 controls (Pastrello et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Two common genetic variations of the miRNAs miR-146a and miR-196a2 have been observed, and have association with pathogenesis of multiple-type diseases Shen et al, 2015;Xu and Tang, 2015;Nikolić et al, 2015). Up to now, only three studies have reported a relationship between miR-146a and miR-196a2 polymorphisms and susceptibility to ovarian cancer (Shen et al, 2008;Pastrello et al, 2010;Liu et al, 2015). Therefore, we investigated further the relationship of miR-146a and miR-196a2 genetic variations with the susceptibility to ovarian cancer.…”

Section: Introductionmentioning

confidence: 98%

miR-146a and miR-196a2 polymorphisms in ovarian cancer risk

Sun¹,

Zhang²,

Tong³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. We investigated the relationship between miR-146a and miR-196a2 genetic polymorphisms and development of ovarian cancer in a Chinese population. A total of 134 patients and 227 control subjects were involved in our study between January 2012 and October 2014 from China-Japan Union Hospital of Jilin University. Genotyping of miR-146a and miR-196a2 was accomplished by polymerase chain reaction coupled with restriction fragment length polymorphism analysis. Unconditional multiple-logistic regression analysis indicated that the GG genotype of miR-146a was associated with an increased risk of ovarian cancer when compared to the CC genotype, and the adjusted OR (95%CI) was 3.73 (1.79-7.80). Moreover, the CG+GG genotype of miR-146a was associated with an increased risk of ovarian cancer compared with the CC genotype (OR = 1.68, 95%CI = 1.06-2.66), and the GG genotype had a higher risk of ovarian cancer than the CC+CG genotype (OR = 3.02, 95%CI = 1. 55-5.98). In conclusion, our study suggests that the miR-146a polymorphism is associated with 2 X.C. Sun et al. Genetics and Molecular Research 15 (3): gmr.15038468 increased risk of ovarian cancer and could be used as a biomarker for ovarian cancer susceptibility.

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Association of SNPs in miR-146a, miR-196a2, and miR-499 with the risk of endometrial/ovarian cancer

Cited by 21 publications

References 9 publications

Identification of a novel subgroup of endometrial cancer patients with loss of thyroid hormone receptor beta expression and improved survival

Identification of a novel subgroup of endometrial cancer patients with loss of thyroid hormone receptor beta expression and improved survival

miR-146a and miR-146b in the diagnosis and prognosis of papillary thyroid carcinoma

miR-146a and miR-196a2 polymorphisms in ovarian cancer risk

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