MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation

Abstract

BackgroundMicroRNAs (miRNAs) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Our previous studies have revealed that miR-148a and miR-152 are significantly down-regulated in gastrointestinal cancers. Interestingly, miR-148b has the same "seed sequences" as miR-148a and miR-152. Although aberrant expression of miR-148b has been observed in several types of cancer, its pathophysiologic role and relevance to tumorigenesis are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which miR-148b acts as a tumor suppressor in gastric cancer.ResultsWe showed significant down-regulation of miR-148b in 106 gastric cancer tissues and four gastric cancer cell lines, compared with their non-tumor counterparts by real-time RT-PCR. In situ hybridization of ten cases confirmed an overt decrease in the level of miR-148b in gastric cancer tissues. Moreover, the expression of miR-148b was demonstrated to be associated with tumor size (P = 0.027) by a Mann-Whitney U test. We also found that miR-148b could inhibit cell proliferation in vitro by MTT assay, growth curves and an anchorage-independent growth assay in MGC-803, SGC-7901, BGC-823 and AGS cells. An experiment in nude mice revealed that miR-148b could suppress tumorigenicity in vivo. Using a luciferase activity assay and western blot, CCKBR was identified as a target of miR-148b in cells. Moreover, an obvious inverse correlation was observed between the expression of CCKBR protein and miR-148b in 49 pairs of tissues (P = 0.002, Spearman's correlation).ConclusionsThese findings provide important evidence that miR-148b targets CCKBR and is significant in suppressing gastric cancer cell growth. Maybe miR-148b would become a potential biomarker and therapeutic target against gastric cancer.

Altered expression of miR-152 and miR-148a in ovarian cancer is related to cell proliferation

“…As shown on the miRBase website, miR-152 and miR-148a have the same seed region, which is 2nt-8nt of miRNA, and is considered the most important recognition site (37). Other studies have shown that miR-148a, miR-148b, and miR-152, all from the same family, have the same seed sequences as well, and also regulate the same target, namely CCKBR, in gastric cancer (38). Stumpel et al also demonstrated that miR-148 and miR-152 have the same seed sequence, and target DNMT1 together (39).…”

CCN5/WISP-2: A micromanager of breast cancer progression

“…Many small non-coding RNAs (micro-RNAs), counterpart of transcriptome, are among the greatest surprises. They have been identified with both biological functions (Lu et al 2005), as well as pathobiological functions including the regulation of tumorigenesis in various organs through modulation of oncogenic or tumor suppressor pathways (Esquela-Kerscher and Slack 2006; Calin and Croce 2006a, b;Blenkiron et al 2007;Ma and Weinberg 2008;Ventura and Jacks 2009;Xiang and Wu 2010;Yu et al 2010;Farazi et al 2011;Song et al 2011). In 2007, Weingberg's laboratory identified micro RNA (miRNA) miR-10b, which plays a critical role in micro-invasion and metastasis of breast cancer cells (Ma et al 2007), and therefore they anticipated a therapeutic importance of miR10b in inhibition of metastatic growth of breast cancer (Ma et al 2010).…”

Aberrant hypermethylation ofmiR-9genes in gastric cancer

“…Recent studies have indicated that several miRNAs, including miR-34b/c, miR-129, miR-137, miR-181C, miR-199a, miR-212, miR-512 and miR-516, were dysregulated and showed aberrant methylation patterns in gastric cancer cells. 6,9,[14][15][16][17][18][19][20][21] The three pri-miR-9 transcripts are all located within non-protein coding transcripts (Fig. 2A).…”