MiR-214 regulates oral cancer KB cell apoptosis through targeting RASSF5

Abstract

ABSTRACT. Ras association domain family member 5 (RASSF5), a member of the Ras association domain family, induces cell apoptosis by phosphorylating FOXO3a, which triggers target gene BIM (proapoptotic factor) activation. MiR-214 is overexpressed in oral cancer tissue, indicating its possible involvement in oral cancer pathogenesis. Bioinformatics analysis has revealed a complimentary sequence between miR-214 and the 3'-UTR of RASSF5 mRNA. However, whether miR-124 regulates RASSF5 in oral cancer remains poorly understood. We aimed to investigate the role of miR-214 in RASSF5 expression regulation in oral cancer. Tumor and paracarcinoma tissues were obtained from 48 oral cancer patients to examine miR-214 and RASSF5 expression. The relationship between miR-214 and RASSF5 was investigated by dual luciferase reporter gene assay. Oral cancer KB cells were cultured in vitro and divided into inhibitor NC, miR-214 inhibitor, Scramble-pMD18, RASSF5-pMD18, and miR-214 inhibitor + RASSF5-pMD18 groups. Caspase 3 activity, cell apoptosis, and total protein expression were measured by spectrophotometry, flow cytometry, and western blot, respectively. MiR-214 expression was significantly increased, while that of RASSF5 decreased in oral cancer tumor tissues compared to paracarcinoma tissues. Luciferase assay showed that miR-214 suppressed RASSF5 expression by targeting its 3'-UTR. Down-regulation of miR-214 and/or enhancement of RASSF5 expression markedly increased FOXO3a phosphorylation, BIM expression, caspase 3 activity, and apoptosis. In conclusion, miR-214 expression was elevated and RASSF5 was down-regulated in oral cancer. Moreover, miR-214 regulated KB cell apoptosis through targeted inhibition of RASSF5 expression, FOXO3a phosphorylation, and BIM expression, suggesting its possible application as a novel therapeutic oral cancer target.

miR‐199a‐3p and miR‐214‐3p improve the overall survival prediction of muscle‐invasive bladder cancer patients after radical cystectomy

“…Moreover, it is of particular interest that the second relevant prognostic mature miRNA in our study, miR‐214‐3p, derives from the stem loop sequence of mir‐214 that clusters with mir‐199a‐2 of the same chromosome locus 1q24.3. Similar to miR‐199a‐3p, miR‐214‐3p acts, depending on the cancer types, oncogenic in osteosarcoma and oral cancer but tumor suppressive in breast, cervical, esophageal, and bladder cancers . Based on our previous expression study , Wang et al.…”

Reduced miR‑202 levels enhanced oral cancer development via targeting Sp1

“…On one hand, miRs can promote the degradation of target gene mRNA at the posttranscriptional level; on the other hand, they can inhibit gene translation and eventually lead to the silencing of the target gene (3,7). According to the different targeting effects, miRs can act as oncogenes or tumor suppressor genes in the progression of a number of malignant tumors (8). miRs have their own specific expression profiles in different tissues and are abnormally expressed in different tumors, resulting in their gradual application as prognostic indicators of cancer (9).…”

Down-Regulation of MicroRNA-214 Contributed to the Enhanced Mitochondrial Transcription Factor A and Inhibited Proliferation of Colorectal Cancer Cells

“…Cellular Physiology and Biochemistry and pancreatic cancer and its down-regulation resulted in the inhibition of cell apoptosis [27,28]. However, recent report suggested that miR-214 was down-regulated in cervical tumor tissues and cancer cells, and up-regulation of miR-214 leaded to the inhibition of cell growth, migration and invasion of cervical cancer cells and prompted the sensitivity to cisplatin [29,30].…”

“…Furthermore, this study discovered that miR-214 overexpression suppressed the proliferation of CRC cells. Numerous studies have provided the evidence that miR-214 could changed biological functions of different cancer cells by its targets such as fibroblast growth factor receptor 1 (FGFR1), forkhead box M1 (FOXM1), Ras association domain family member 5 (RASSF5), Plexin-B1, phosphatase and tensin homolog (PTEN), and Ring finger and WD domain 2 (RFWD2) [27][28][29][30][31][32][33][34][35]. TFAM is a molecule which is essential for mtDNA replication and transcription, as well as mtDNA maintenance [36,37].…”