miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL

Abstract

Mounting evidence has shown that microRNAs (miRNAs), a class of small non-coding RNAs, are frequently deregulated in human malignancies and have pivotal roles in diverse biological processes including cancer cell proliferation. Herein, we investigated the expression pattern of miR-383 in 64 hepatocellular carcinoma (HCC) tissues and 4 HCC cell lines and found that miR-383 was downregulated in HCC tissues and cell lines. Moreover, miR-383 expression in HCC was significantly correlated with tumor size and tumor-node-metastasis (TNM) stage. Kaplan-Meier analysis showed that decreased miR-383 expression was associated with poor overall survival of HCC patients. In addition, Cox regression analysis indicated that miR-383 was an independent prognostic factor for HCC patients. Then, functional studies demonstrated that ectopic miR-383 expression could significantly suppress the in vitro proliferation of HCC cells, as well as induce cell cycle arrest and cell apoptosis. Luciferase reporter assay further identified that a proliferation-inducing ligand (APRIL), a member in the tumor necrosis factor (TNF) superfamily, was a novel target gene for miR-383. Subsequent investigation revealed that miR-383 expression was inversely correlated with APRIL messenger RNA (mRNA) expression in HCC tissues. Besides, recombinant human APRIL (rhAPRIL) could rescue HCC cell proliferation inhibited by miR-383. Taken together, our present study provided the first evidence that miR-383 was decreased in HCC and associated with tumor progression and prognosis of HCC patients. Furthermore, our findings confirmed that miR-383 might inhibit HCC cell proliferation partially via downregulating APRIL expression. Thus, this study might provide a promising strategy by targeting with the miR-383-APRIL axis in the treatment of HCC.

Redox Regulating Enzymes and Connected MicroRNA Regulators Have Prognostic Value in Classical Hodgkin Lymphomas

“…In gastric cancer miR-23b associated with unfavorable survival [52]. The existing evidence from miR-383 suggests its tumor-suppressing role in vitro, for example, hepatocellular, pancreatic, and esophageal carcinomas [53–55]. This is in contradiction with our results, which suggested both miR-23b and miR-383 act clearly oncogenic in Hodgkin lymphomas.…”

Prognostic and predictive roles of microRNA-383 in colorectal cancer

“…It has also been revealed by the recent studies that low levels of miR-383 were correlated with high levels of APRIL expression in clinical HCC samples. 16 Overall, the conclusions obtained from the recent studies show that miR-383 has a critical role in cell cycle regulation, proliferation, and apoptosis in cancer. However, its functional and regulatory roles in all human cancers have not been clearly elucidated yet.…”

“…This miRNA has been found to be down regulated in testicular embryonic carcinoma, hepatocellular carcinoma, glioma, medulloblastoma, 15,16 breast cancer, 17 and ependymoma. 18 Results of a study showed that exposure to UV led to a significantly lower expression of miR-383 in A431cells (a model human cell line of epidermoid carcinoma).…”

Chicken gga-miR-130a targets HOXA3 and MDFIC and inhibits Marek’s disease lymphoma cell proliferation and migration

“…The target mRNA molecules are then silenced by one or more of the following processes: cleavage of the mRNA strand into two pieces, destabilization of the mRNA through shortening of its polyA tail, and preventing translation of mRNA into protein [9,10]. As important regulatory molecules, miRNAs are involved in multiple cellular processes, including development [11][12][13], proliferation [14][15][16][17], migration [16,[18][19][20], and apoptosis [17,21,22]. Studies have demonstrated that miRNAs are linked with various cancers and tumors in humans [23][24][25][26].…”