MicroRNA-182 Promotes Tumor Cell Growth by Targeting Transcription Elongation Factor A-like 7 in Endometrial Carcinoma

Abstract

Background/Aims: Endometrial carcinoma (EC) is the most common gynecological malignancy among women worldwide. Despite its prevalence, the molecular mechanisms underlying endometrial carcinogenesis are poorly understood. The purpose of this study was to examine the role of microRNA-182 and its target gene transcription elongation factor A-like 7 (TCEAL7) in EC. Methods: The expression of miR-182 in human normal endometrial epithelial cells (NEEC) and in three human endometrial carcinoma cell lines (HEC-1B, RL95-2 and AN3CA) was measured by qRT-PCR, and the mRNA and protein expression of TCEAL7 were assessed in the same three endometrial carcinoma cell lines and NEEC by qRT-PCR and western blotting, respectively. Subsequently, the target of miR-182 was predicted by bioinformatics and confirmed using a luciferase assay. Cell proliferation and colony formation of RL95-2 cells were examined by MTT assay and crystal violet staining, respectively. The expression of NFκB-p65, c-Myc and cyclin D1 proteins was determined by Western blot analysis. Results: MiR-182 was significantly upregulated and TCEAL7 was downregulated in EC cell lines compared to NEEC. We showed that MiR-182 binds directly to a conserved 8 bp sequence in the 3'-UTR of TCEAL7, and inhibition of miR-182 upregulated TCEAL7 mRNA and protein expression to levels comparable to those induced by lentiviral-mediated overexpression of TCEAL7. MiR-182 inhibition decreased cell proliferation and colony formation ability, downregulated the expression of the pro-proliferative genes c-Myc and cyclin D1, and inhibited NFκB activation, and these effects were mimicked by TCEAL7 overexpression. Conclusions: miR-182 acts as an oncogenic miRNA in EC, promoting cell proliferation by targeting the tumor suppressor gene TCEAL7 and modulating the activity of its downstream effectors c-Myc, cyclin D1 and NFκB.

Adiponectin and Endometrial Cancer: A Systematic Review and Meta-Analysis

“…Besides its intimate involvement in the regulation of metabolism, adiponectin has been shown in a series of in vitro studies that inhibits the proliferation of several cancer-derived cell-types such as breast cancer, endometrial cancer, prostate cancer and colorectal cancer [7][8][9][10][11][12][13][14][15]. The suppressive effects on these cancers may involve AMPK-mediated or non-AMPK-mediated modulation of mTOR-S6K, PI3K-AKT, JUN-STAT3 and MAPK signaling pathways, suggesting that adiponectin may play a direct role in tumor development and growth [3,[16][17][18].…”

Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition

“…Cell viability was calculated by Cell Counting Kit-8 (CCK8) assay according to the manufacturer’s protocol [20]. Ishikawa and HEC-1-B cells were seeded into a 96-well plate and then cultured with serum-free medium (Ishikawa 2000 cells/well, HEC-1-B 1600 cells/well).…”

Expression Profiles of Endometrial Carcinoma by Integrative Analysis of TCGA Data

“…Endometrial carcinoma (EC) is currently the most common gynecological malignancy and the seventh most common form of cancer among women worldwide [1,2] . Histologically, EC can be divided into 2 subtypes [3] : estrogen-dependent type I EC and gene-mutated type II EC.…”

“…Despite its prevalence, the molecular mechanisms underlying EC are poorly understood [1] . Therefore, studies on genes and miRNAs expression and an understanding of the mechanism involved in EC are needed for effective diagnosis, therapy and prevention.…”

“…Recent studies have shown that EC is also associated with miRNAs. For example, miR-182 acts as an oncogenic miRNA in EC, promoting cell proliferation by targeting the tumor suppressor gene TCEAL7 and modulating the activity of its downstream effectors c-Myc, cyclin D1 and NFκB [1] .…”