miR-203 Functions as a Tumor Suppressor by Inhibiting Epithelial to Mesenchymal Transition in Ovarian Cancer

Abstract

Objective Ovarian cancer is a gynecological malignancy that has a high mortality rate in women due to metastatic progression and recurrence. miRNAs are small, endogenous, noncoding RNAs that function as tumor suppressors or oncogenes in various human cancers by selectively suppressing the expression of target genes. The objective of this study is to investigate the role of miR-203 in ovarian cancer. Methods miR-203 was expressed in ovarian cancer SKOV3 and OVCAR3 cells using lentiviral vector and cell proliferation, migration, invasion were examined using MTT, transwell and Matrigel assays, respectively. Tumor growth was examined using Xenograft mouse model. Results miR-203 expression was downregulated, whereas expression of its target gene Snai2 was upregulated in human ovarian serous carcinoma tissue as compared to normal ovaries. In addition, high miR-203 expression was associated with long-term survival rate of ovarian cancer patients. miR-203 overexpression inhibited cell proliferation, migration, and invasion of SKOV3 and OVCAR3 ovarian cancer cells. Furthermore, miR-203 overexpression inhibited the epithelial to mesenchymal transition (EMT) in ovarian cancer cells. Silencing Snai2 with lentiviral short hairpin (sh) RNA mimics miR-203-mediated inhibition of EMT and tumor cell invasion. Xenografts of miR-203-overexpressing ovarian cancer cells in immunodeficient mice exhibited a significantly reduced tumor growth. Conclusion miR-203 functions as a tumor suppressor by down regulating Snai2 in ovarian cancer.

MiRNA203 suppresses the expression of protumorigenic STAT1 in glioblastoma to inhibit tumorigenesis

“…While STAT1 expression is markedly lower in cells with enforced miR203 expression, both STAT2 and STAT3 are unaffected by miR203 expression (Figure 4A). Moreover, while STAT1 was a miR203 target gene in GBM cells, as shown in Figure 4B Snai2/Slug was not consistently silenced by miR203 expression in GBM cells, although it was targeted by miR203 in ovarian cancer cells [34]. This finding is also consistent with our previous findings that miRNAs silence gene expression in a cell-type specific manner.…”

“…While oncogenic miRNAs have been studied in depth, tumor suppressor miRNAs which tend to be underexpressed in cancer have been relatively poorly characterized. We recently identified miR203 to have tumor suppressive activity in ovarian cancer by targeting Slug/snail2 and inhibiting epithelial to mesenchymal transition [34]. In the present study we found that miR203 was expressed at especially low levels in GBM.…”

miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway

“…We previously demonstrated that miR-203 is a tumor suppressor miRNA in ovarian cancer and that miR-203 expression inhibits tumor growth by targeting transcription factor Snai2 [ 23 ]. We also showed that BIRC5/survivin was highly expressed in ovarian cancer but not in the normal ovary tissues.…”

The Role of microRNAs in Epithelial Ovarian Cancer Metastasis

“…However, inconsistent findings have also been reported. For example, miR-124-3p, miR-148a-3p, miR-203a, and miR-375 were detected exhibiting differential expression in EOC specimens with both downregulation and upregulation [ 114 , 116 , 117 , 118 , 119 ]. Several other miRNAs listed in Table 1 have also been shown to be either up- or down-regulated in different studies.…”

“…Overexpression of miR-101-3p, miR-130b, and miR-1236-3p inhibits EOC cell invasion and migration, increases E-cadherin, and decreases mesenchymal markers by directly targeting ZEB1 [ 165 , 168 , 178 ]. Similarly, SNAI1 and SNAI2 are targets of multiple miRNAs [ 119 , 167 , 175 , 222 ]. Using the TCGA database and tissue samples from EOC patients, Yang et al identified miR-506 as a positive prognostic predictor of EOC patients [ 222 ].…”