Abstract
BackgroundAn increasing amount of evidence has revealed that microRNAs regulate various biological processes, including cell differentiation, cell proliferation, apoptosis, drug resistance, and fat metabolism. Studies have shown that miR-93’s targetome in cancer has not been fully defined. Moreover, the role of miR-93 in epithelial ovarian carcinoma (EOC) remains largely unknown.MethodsMIR-93 mRNA expression in normal ovarian tissue, benign tumors, borderline tumors, primary ovarian carcinomas, and metastatic omentum was quantified. The ovarian carcinoma cell lines OVCAR3, SKOV3/DDP, and HO8910-PM were transfected with miR-93-5P, after which cell phenotype and expression of relevant molecules were assayed. Dual-luciferase reporter assay and a xenograft mouse model were used to examine miR-93 and its target gene RHOC (Ras homolog gene family member C).ResultsMIR-93 mRNA expression was significantly lower in ovarian carcinomas and borderline tumors than in normal ovarian tissues (p < 0.05), and was lower in metastatic omentum than in relative primary ovarian carcinomas (p < 0.05). MIR-93 mRNA expression was also negatively associated with differentiation (well vs. poor and moderate) and International Federation of Gynecology and Obstetrics staging (FIGO stage I/II vs. stage III/IV) in ovarian carcinoma (p < 0.05), besides, miR-93 was higher expressed in mucinous adenocarcinoma than the other types (p < 0.05). MiR-93-5P overexpression reduced proliferation (p < 0.05); promoted G1 or S arrest and apoptosis (p < 0.05); suppressed migration and invasion (p < 0.05); and reduced RhoC, P70S6 kinase, Bcl-xL, matrix metalloproteinase 9 (MMP9) mRNA or protein expression; conversely, it induced P53 and cleaved PARP expression (p < 0.05). Dual-luciferase reporter assay indicated that miR-93 directly targeted RhoC by binding its 3′ untranslated region. MiR-93-5P transfection also suppressed tumor development and RhoC expression (determined by immunohistochemistry) in vivo in the xenograft mouse model (p < 0.05).ConclusionsThis is the first demonstration that miR-93-5P may inhibit EOC tumorigenesis and progression by targeting RhoC. These findings indicate that miR-93-5P is a potential suppressor of ovarian cellular proliferation. The involvement of miR-93-5P–mediated RhoC downregulation in inhibiting EOC aggressiveness may provide extended insight into the molecular mechanisms underlying cancer aggressiveness.
Highlights
An increasing amount of evidence has revealed that microRNAs regulate various biological processes, including cell differentiation, cell proliferation, apoptosis, drug resistance, and fat metabolism
Correlation of MIR93 mRNA expression with ovarian carcinoma pathogenesis and aggressiveness MiR-93 was quantified in normal ovary tissue, benign and borderline tumors, and primary ovarian carcinoma using real-time PCR
MIR93 mRNA expression was significantly lower in ovarian carcinomas and borderline tumors than in normal ovarian tissues, and lower in metastatic omentum than in relative primary ovarian carcinomas (Figure 1A, p < 0.05), and was negatively associated with International Federation of Gynecology and Obstetrics (FIGO) staging, differentiation and pathological subtype in ovarian carcinoma
Summary
An increasing amount of evidence has revealed that microRNAs regulate various biological processes, including cell differentiation, cell proliferation, apoptosis, drug resistance, and fat metabolism. The role of miR-93 in epithelial ovarian carcinoma (EOC) remains largely unknown. The primary genetic alterations associated with epithelial ovarian cancer, which accounts for 90% of ovarian cancer, remain to be identified [1]. As recurrence and metastasis greatly affect the prognosis of ovarian cancer, the 5-year survival rate for all stages of ovarian cancer has been estimated to be 35–38%. Due to the high mortality of epithelial cancer, exploring the related molecular mechanisms of epithelial ovarian carcinoma (EOC) initiation and development, and identifying the major factors of invasion and metastasis would be of great significance for the treatment and prognosis of EOC. Upregulated RhoC may affect ovarian carcinogenesis and should be considered a good biomarker of ovarian carcinoma differentiation and progression. Most studies show that RhoC has multiple functions in tumor metastasis, orchestrating the action of multiple downstream effectors, degradation, and reconstruction of the extracellular matrix
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
