microRNA-148a inhibits hepatocellular carcinoma cell invasion by targeting sphingosine-1-phosphate receptor 1

Abstract

microRNA (miR)-148a has been shown to act as an important suppressor in numerous human malignancies and is markedly downregulated in hepatocellular carcinoma; however, the role of miR-148a in the regulation of hepatocellular carcinoma cell invasion, as well as the underlying mechanism, has never been studied. In the present study, the expression level of miR-148a was found to be significantly decreased in hepatocellular carcinoma tissues and HepG2 cells when compared with that in the normal adjacent tissues. Furthermore, a novel target of miR-148a was found, sphingosine-1-phosphate receptor 1 (S1PR1), whose expression was negatively regulated by miR-148a at a post-transcriptional level in hepatocellular carcinoma HepG2 cells. Upregulation of miR-148a by transfection with miR-148a mimics notably suppressed HepG2 cell invasion, similar to the effect of the SIPR1 downregulation induced by SIPR1-specific small interfering RNA, while the restoration of S1PR1 expression reversed the inhibitory effect of miR-148a upregulation on HepG2 cell invasion. Accordingly, the current study suggests that miR-148a plays an inhibitory role in the regulation of hepatocellular carcinoma cell invasion by directly targeting S1PR1.

miR-148a increases the sensitivity to cisplatin by targeting Rab14 in renal cancer cells

“…Downregulation of miR-148a has been identified in various types of human cancer, including gastric cancer, breast cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, and is therefore considered a tumor-suppressive miRNA (18)(19)(20)(21). Moreover, miR-148a overexpression sensitized the cancer cells to anticancer drugs.…”

The role of the miR‐148/‐152 family in physiology and disease

“…The Twist1/miR-148a/Bim regulatory pathway might be responsible for the persistence of such pathogenic Th1 lymphocytes in the inflamed tissues of patients with chronic inflammatory diseases (rheumatic diseases, Crohn's disease and ulcerative colitis) despite state-of-the-art immunosuppressive therapies [50]. Moreover other miR-148a targets than Bcl2l11 could contribute to the inflamed tissue residency of the Th1 lymphocytes, including the sphingosine-1-phosphate receptor 1 [45,52], which regulates the migration of lymphocytes [53]. In addition to its significant role in regulating T lymphocyte function, miR-148a plays a key role in the regulation and differentiation of B lymphocytes [25].…”

MicroRNA-148a inhibits migration of breast cancer cells by targeting MMP-13

“…MiR-148a inhibits the metastasis and invasion of hepatocellular carcinoma and gastric carcinoma [9,10], regulates the differentiation of breast cancer [11] and suppresses the growth of pancreatic cancer and colorectal carcinoma [12,13]. It is reported that miR-148a is expressed at low level in breast cancer [14] and is associated with the angiogenesis and growth of breast cancer [14].…”