miR-203 regulates the proliferation, apoptosis and cell cycle progression of pancreatic cancer cells by targeting Survivin

Abstract

MicroRNAs have emerged as crucial regulators of tumorigenesis. However, the mechanism by which miR‑203 is involved in the pathogenesis of pancreatic cancer (PC) remains elusive. In the present study, PC cell lines were used as an experimental model to investigate the expression and functional role of miR‑203 in PC. miR‑203 mimic virus, miRNA negative control virus and Survivin shRNA virus were transfected into the PC cell line, CFPAC‑1. mRNA and protein levels of Survivin were detected using qPCR and western blot analysis. Proliferation, apoptosis and cell cycle profiles were detected by an MTT assay and flow cytometry. Female BALB/cA‑nu nude mice were used to validate the role of miR‑203 in vivo. The protein levels of Survivin were found to negatively correlate with miR‑203 levels in four PC cell lines. A luciferase assay revealed that Survivin was a direct target of miR‑203. Transfection with miR‑203 mimic inhibited CFPAC‑1 cell proliferation and induced apoptosis and G1 phase cell cycle arrest, similar to knockdown of Survivin. In the in vivo nude mouse model, the downregulation of Survivin by knockdown of Survivin or transfection with miR‑203 mimic inhibited tumor growth. Results of the current study indicate that miR‑203 regulates the proliferation, apoptosis and cell cycle progression of PC cells by targeting Survivin.

MicroRNAs in pancreatic malignancy: Progress and promises

“…Mechanistically, it was demonstrated that miR-96 imparted its effect by inhibiting K-RAS and Akt signaling [26]. In a recent study, Xu et al [27] demonstrated the potential of miR-203 in the inhibition of Survivin, which is overexpressed in majority of cancers, including pancreatic cancer and plays a role in cytoprotection, apoptosis resistance and cell-cycle regulation. Their study showed that overexpression of miR-203 effectively induced apoptosis, inhibited cell proliferation and caused cell cycle arrest.…”

“…Their study showed that overexpression of miR-203 effectively induced apoptosis, inhibited cell proliferation and caused cell cycle arrest. Furthermore, in vivo study also demonstrated a potent effect of miR-203 on tumor growth inhibition [27]. Farhana et al [28] provided evidence that modulation of miR-150* and miR-630 expression resulted in diminished cellular growth and induced apoptosis.…”

Dietary Intervention by Phytochemicals and Their Role in Modulating Coding and Non-Coding Genes in Cancer

“…The same effect is attributed to miR-34a in pancreatic cells [136]. miR-203 overexpression inhibited pancreatic cell proliferation [137] and tumour growth in a mouse model [138]. miR-17-92 is an oncogenic cluster [139,140,141], but also a tumour suppressor [142].…”

The functional role of microRNAs in laryngeal carcinoma

“…Survivin has little or no expression in normal cells but has high expression in a variety of tumor cells. Survivin is a specific target molecule of miR-203 [20]. After transfecting miR-203, the expression of survivin will be downregulated, which will induce cell apoptosis, inhibit cell proliferation, and reduce tumor invasion [21].…”

“…However, the molecular mechanism of laryngeal cancer is still unclear. MicroRNA (miRNA) is a small molecule non-coding RNA with a length of about [19][20][21][22][23][24][25] nucleotides that regulates gene expression by binding to messenger RNA, leading to transcript degradation or translational inhibition [9]. Bioinformatics analysis predicts that miRNA regulates more than 30% of protein-coding genes.…”