MiR-935 Promotes Clear Cell Renal Cell Carcinoma Migration and Invasion by Targeting IREB2

Clear cell renal cell carcinoma (ccRCC) has the highest rate of metastasis and invasion in RCC and is the third most common adult urinary malignancy. miRNA may serve a critical role in human cancer development and progression, has been confirmed to play a pivotal role in RCC cell invasion and migration. Since miR‑935 had been verified to be an oncogene or tumor suppressor in various cancers, the role of miR‑935 in RCC was unclear.

Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify miR-935 expression. CCK-8 assay, wound healing assay and transwell assay were used to investigate the cell proliferation, migration and invasion of miR-935. Receiver operating characteristic (ROC) curve analysis was applied to discriminate different clinical classifications. Gain or loss of function approaches were used to investigate the cell proliferation, migration and invasion of miR-935 in vitro. Bioinformatics analysis and dual-luciferase reporter assay were used to identify the target of miR-935.

MiR-935 had a higher expression level in RCC cells and cancer tissues. MiR-935 mimics promoted cell proliferation, migration and invasion, and miR-935 inhibitor inhibited cell inhibit malignancy of cancer cells. Bioinformatics analysis and dual-luciferase reporter assay identified iron-responsive element-binding protein 2 (IREB2) as a direct target of miR-935. qRT-PCR showed IREB2 expression was downregulated in ccRCC cancer tissues and high IREB2 expression had a longer overall survival (OS) and disease-free survival (DFS). Silencing IREB2 could reverse the function of miR-935 inhibitor on cell proliferation and metastasis in renal cancer cells.

The study indicated that miR-935 may act as an oncomiRNA and influenced migration and invasion progress of ccRCC by targeting IREB2. Oncogene miR-935 may be a molecular marker and uncover new strategies for ccRCC.