MicroRNA-205 promotes cell invasion by repressing TCF21 in human ovarian cancer

Abstract

BackgroundOvarian cancer is the leading lethal, gynecological malignancy in the United States. No doubt, the continued morbidity and mortality of ovarian cancer reflects a poor understanding of invasive mechanisms. Recent studies reveal that ovarian cancers express aberrant microRNAs (miRNAs or miRs), some of which have oncogenic or tumor suppressor properties. Several studies suggested that miR-205 is involved in tumorigenesis. Presently, we investigate the molecular mechanisms and target of miR-205 in ovarian cancer.MethodsQuantitative real-time polymerase chain reaction and western blot were performed to assess miR-205 and transcription factor 21 (TCF21) expression in ovarian cancer and normal ovary samples. The effect of miR-205 on TCF21 was determined by luciferase reporter assay and western blot. The effect of miR-205 and TCF21 on cell invasion was quantitated using transwell invasion assay.ResultmiR-205 expression was increased in ovarian cancer and it promoted the invasive behavior of ovarian cancer cell lines (OVCAR-5, OVCAR-8 and SKOV-3). miR-205 directly targeted TCF21, which was significantly decreased in ovarian cancer tissue. miR-205 inhibited TCF21 expression and as a consequence blunted the inhibitory effect of TCF21 on cell invasion. Matrix Metalloproteinases (MMPs) play an important role in cancer invasion and metastasis. TCF21 inhibited MMP-2 and MMP-10 and decreased ovarian cancer cell invasion. Co-transfection of TCF21 expression plasmid with miR-205 mimic diminished the inhibitory effect of TCF21 on MMP-2 and MMP-10 in ovarian cancer cells.ConclusionmiR-205 appears to have an important role in the spread of ovarian cancer by targeting TCF21. These findings offer a new mechanism of ovarian cancer tumorigenesis, which could be useful for the development of new therapeutic approaches to ovarian cancer treatment.

MicroRNA-1271-5p inhibits the tumorigenesis of ovarian cancer through targeting E2F5 and negatively regulates the mTOR signaling pathway

“…And miR-1 inhibited cell migration and proliferation in OC through c-Met pathway [10]. But miR-205 accelerated cell invasion by repressing TCF21 in human OC [11]. And miR-216a facilitated the metastasis and EMT of OC by suppressing the PTEN/AKT pathway [12].…”

Bioinformatics Analysis of Prognostic value and prospective Pathway signal of miR-30a in Ovarian Cancer

“…Duan et al and others (34) found that TCF21 can target PI3K/Akt and ERK signal pathways, thus inhibiting tumor-associated angiogenesis and cholangiocarcinoma growth. Many evidences show that TCF21 is regulated by miRNAs, such as miR526b (35), miR-205 (36), which can inhibit tumor development. Zhou et al (37) found that microRNA-30-3p targeting TCF21 inhibited endothelial cell injury induced by in ammatory factors.…”

Prognostic Values and Prospective Pathway Signaling of miR-30a in Ovarian Cancer: A Study Based on Gene Expression Omnibus and Bioinformatics Analysis

“…Duan et al and others (34) found that TCF21 can target PI3K/Akt and ERK signal pathways, thus inhibiting tumor-associated angiogenesis and cholangiocarcinoma growth. Many evidences show that TCF21 is regulated by miRNAs, such as miR526b (35), miR-205 (36), which can inhibit tumor development. Zhou et al (37) found that microRNA-30-3p targeting TCF21 inhibited endothelial cell injury induced by inflammatory factors.…”