miR-93-3p inhibition suppresses clear cell renal cell carcinoma proliferation, metastasis and invasion

Abstract

miRNA dysregulation is associated with many human diseases, including cancer. This study explored the effects of miR-93-3p on clear cell renal cell carcinoma (ccRCC). We found that miR-93-3p is upregulated an average of 38-fold in 138 ccRCC specimens compared to matched normal kidney tissues, which correlated with poor patient outcome. miR-93-3p inhibition reduced ccRCC cell growth, invasion, and migration in vitro and in a mouse xenograft model. A search of the TargetScan, miRanda, and PicTar databases revealed that miR-93-3p is predicted to regulate pigment epithelium-derived factor (PEDF). A direct PEDF-miR-93-3p interaction was confirmed via dual-luciferase reporter assays. Like miR-93-3p inhibition, PEDF overexpression induced cell apoptosis and inhibited migration and invasion. Additionally, co-transfection with PEDF siRNA reversed the effects of miR-93-3p inhibition in ccRCC cells. Thus, miR-93-3p is a likely ccRCC oncogene that acts by regulating PEDF. These results suggest that miR-93-3p may predict ccRCC patient clinical outcome and serve as a novel anti-ccRCC therapeutic target.

RETRACTED: Long noncoding RNA ZNF667‐AS1 reduces tumor invasion and metastasis in cervical cancer by counteracting microRNA‐93‐3p‐dependent PEG3 downregulation

“…Anticancer ZNF238 is repressed by miR‐20b overexpression whereas ZNF24, a tumor promoter, is increased by miR‐940 dysregulation (Lu et al , ). In clear cell renal cell carcinoma cells, miR‐93‐3p was found to decrease the expression of pigment epithelium‐derived factor (PEDF) and inhibit osteogenesis (Wang et al , ). As a single miRNA can distinctively alter the expression of multiple mRNA transcripts (Hu et al , ; Li et al , ), we hypothesized that miR‐93‐3p dysregulation is closely related to CC cell behavior.…”

“…As a class of small noncoding RNAs, microRNAs (miRNAs) play significant roles in post‐transcriptional gene regulation by targeting the 3′UTR of target messenger RNAs (mRNAs) and decreasing the stability and/or translation of these mRNAs (Bei et al , ). MiRNA dysregulation and its effects have been observed in a variety of human diseases, and various miRNAs can function as potential candidates for CC treatment and prognosis (Liang et al , ; Wang et al , ; Zhou et al , ). In particular, miR‐93 is reported to be involved in CC metastasis and invasion (Wang et al , ).…”

Molecular mechanism and role of microRNA‐93 in human cancers: A study based on bioinformatics analysis, meta‐analysis, and quantitative polymerase chain reaction validation

“…Separately, 11 studies from eight articles 15,[56][57][58][59][60][61][62] were included in the diagnostic meta-analysis and 14 studies from 13 articles 15,24,29,41,47,51,[63][64][65][66][67][68][69] were included in the prognostic meta-analysis. After screening the titles and abstracts, 476 articles were excluded because they were reviews (n = 18), meta-analyses (n = 5), nonhuman studies (n = 14), or studies irrelevant to our topic (n = 439).…”

miR‐452 promotes cell metastasis and the epithelial to mesenchymal by targeting SOX7 in clear‐cell renal‐cell carcinoma

“…miRNAs regulate RNA degradation or translation by binding to target mRNA 3′‐UTR at the posttranscriptional level . A number of studies have shown that several miRNAs act as oncogenes in ccRCC, including miR‐566, miR‐93, miR‐195, and miR‐429 . miR‐452 is also upregulated and acts as an oncogene in several cancers .…”