miR-615-3p promotes proliferation and migration and inhibits apoptosis through its potential target CELF2 in gastric cancer

Abstract

Gastric cancer incidence is relatively higher in China than that in developed countries; however, molecular mechanisms considering the initiation and progression of gastric cancer are still unclear. For decades, numerous microRNAs have been found to regulate a wide range of biological functions in gastric cancer. However, the oncogenic function of miR-615-3p in gastric cancer has not been reported to date. With the help of gene and microRNA chips in 10 patients, we were able to screen differential expressed genes and microRNAs compared with normal gastric tissues. After that, online bioinformatics analysis tools were used to predict microRNAs' potential targets. As a result, miR-615-3p and its potential target, CELF2, were selected for further experiments. QRT-PCR and western blot results indicated the aberrant high expression of miR-615-3p and low expression of CELF2 in gastric cancer both in vivo and in vitro. Moreover, miR-615-3p expression correlated to T and M stage. Up regulation of miR-615-3p inhibited the apoptosis, promoted proliferation and migration and led to the down-regulation of CELF2. Meanwhile, down-regulation of miR-615-3p resulted in anti-tumor effects. Immunochemistry staining of CELF2 showed its association with T, N and M stage. In addition, overexpression of CELF2 could reverse miR-615-3p's oncogenic functions stated before. These findings indicate that miR-615-3p promotes gastric cancer proliferation and migration by suppressing CELF2 expression for the first time, providing clues for future clinical practices.

Elevated miR-615-3p Expression Predicts Adverse Clinical Outcome and Promotes Proliferation and Migration of Prostate Cancer Cells

“…13,14,31 Moreover, dysregulated miR-615-3p expression has previously been reported also in other human cancer types. 32,33 Thus, similar to the finding of elevated miR-615-3p levels in more aggressive PC, miR-615-3p has been found to be up-regulated in hepatocellular carcinoma patients with recurrence compared with patients without recurrence. 32 Moreover, miR-615-3p overexpression in hepatocellular carcinoma and gastric cancer cell lines has been demonstrated to promote cell proliferation and migration, 32,33 similar to the more aggressive phenotypes that were observed herein in PC cells after overexpressing miR-615-3p.…”

“…32,33 Thus, similar to the finding of elevated miR-615-3p levels in more aggressive PC, miR-615-3p has been found to be up-regulated in hepatocellular carcinoma patients with recurrence compared with patients without recurrence. 32 Moreover, miR-615-3p overexpression in hepatocellular carcinoma and gastric cancer cell lines has been demonstrated to promote cell proliferation and migration, 32,33 similar to the more aggressive phenotypes that were observed herein in PC cells after overexpressing miR-615-3p. In contrast, in nonesmall-cell lung cancer, miR-615-3p expression has been identified as down-regulated in tumor samples compared with normal tissue samples and to inhibit cell proliferation and migration in vitro.…”

“…This is in contrast to an earlier finding in gastric cancer cells, where miR-615-3p overexpression inhibited cell apoptosis. 33 Although inhibition of apoptosis is generally viewed as a cancer hallmark, its role in cancer biology is more complex. Indeed, it is also well known that apoptosis can promote division of neighboring cells and drive tumor formation; and tumors often have elevated apoptosis rates, reflecting the increased cell turnover compared with the nonmalignant counterparts.…”

Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis

“…Moreover, miR-193b-3p is a predictive biomarkers of renal cell carcinoma [68]. The high expression of miR-615-3p was associated with pathogenesis of CRC and gastric cancer [69,70].…”

Circular RNA-Centered Regulatory Networks in the Physiopathology of Cardiovascular Diseases

“…In this study, circZNF609 was overexpressed in endothelial cells from diabetes mellitus, hypertension, and coronary artery disease (CAD) patients, and was associated with increased angiogenesis [58]. On the other, circZNF609 was proposed as a potential miRNA sponge by interacting with miR-615, a negative regulator of the myocyte enhancer factor 2A (MEF2A), a transcription factor largely associated with CAD and MI [59]. In fact, in hypoxic and high glucose content conditions, circZNF609 was found to be up-regulated, leading to tube formation, migration of endothelial cells, and triggering programmed cell death.…”