MicroRNA-141 inhibits tumor growth and metastasis in gastric cancer by directly targeting transcriptional co-activator with PDZ-binding motif, TAZ

Abstract

Gastric cancer (GC) is a biologically heterogeneous disease accompanying various genetic and epigenetic alterations, and the molecular mechanisms underlying this disease are complex and not completely understood. Increasing evidence shows that abnormal microRNA (miRNA) expression is involved in GC tumorigenesis, but the role of specific miRNAs involved in this disease remains elusive. MiR-141 was previously reported to act as tumor suppressors or oncogenes in diverse cancers. However, their accurate expression, function and mechanism in GC are largely unclear. Here we found that the expression of miR-141 was significantly reduced in GC compared with paired adjacent normal tissues and was significantly correlated with a more aggressive phenotype of GC in patients. Ectopic expression of miR-141 mimics in GC cell lines resulted in reduced proliferation, invasion and migration, and inhibition of miR-141 in GC cell lines promoted cell proliferation, invasion and migration in vitro. We further demonstrated that miR-141 acted as tumor suppressors through targeting transcriptional co-activator with PDZ-binding motif (TAZ) in GC. Moreover, the inverse relationship between miR-141 and its target was verified in patients and xenograft mice. Finally, overexpression of miR-141 suppressed tumor growth and pulmonary metastasis in nude mice. Take together, we identified that miR-141 is a potent tumor suppressor in the stomach, and its growth inhibitory effects are, in part, mediated through its downstream target gene, TAZ. These findings implied that miR-141 might be employed as novel prognostic markers and therapeutic targets of GC.

Development of a deregulating MicroRNA panel for the detection of early relapse in postoperative colorectal cancer patients

“…Although let-7b upregulation is observed in aged neural stem cells and is associated with the severity of lens opacity during aging [40], we discovered that downregulation of let-7b is an early relapse biomarker, particularly in elderly patients. miR-141 has been reported to inhibit the migration and proliferation of gastric cancer cells [40,41], whereas other studies have shown ); ΔCt = (Ct miR −Ct U6b ), with U6b as the internal control for normalization. a The samples from early relapsed patients showed significantly increased miR-7 expression levels (P = 0.014).…”

Prognostic value of miR-141 downregulation in gastric cancer

“…Previously, Zuo et al (2015) found that the expression of miR-141 was significantly reduced in gastric cancer tissues compared with paired adjacent normal tissues. MiR-141 inhibited tumor growth and metastasis in gastric cancer by directly targeting the transcriptional co-activator with PDZ-binding motif, TAZ.…”

The Roles of MicroRNA-141 in Human Cancers: From Diagnosis to Treatment

“…It was reported that the expression of miR-141 was significantly correlated with a more aggressive phenotype in clinic [49]. That is to say, miR-141 suppressed in vitro migration and invasion of GC cells.…”

“…Therefore, the miR-141-STAT4 pathway may be exploited in a therapeutic approach for the treatment of H. Pylori related cancers [48]. Functional researches suggested that miR-141 could not only inhibit growth and colony formation but also enhance caspase-3-dependent apoptosis in pancreatic ductal adenocarcinomacells by targeting Yes-associated protein-1 [49]. In pancreatic cancer, another research demonstrated that miR-141 could directly bind to 3′-UTR of mitogenactivated protein kinase isoform 4 to inhibit MAP4K4 expression and lead to the inhibition of cell proliferation [50].…”