Prognostic significance of microRNA-141 expression and its tumor suppressor function in human pancreatic ductal adenocarcinoma

Abstract

Increasing evidence shows that dysregulation of microRNAs is correlated with tumor development. This study was performed to determine the expression of miR-141 and investigate its clinical significance in pancreatic ductal adenocarcinoma (PDAC). Taqman quantitative RT-PCR was used to detect miR-141 expressions in 94 PDAC tissues and 16 nontumorous pancreatic tissues. Correlations between miR-141 expression and clinicopathologic features and prognosis of patients were statistically analyzed. The effects of miR-141 expression on growth and apoptosis of PDAC cell line (PANC-1) were determined by MTT, colony formation, and flow cytometry assays. Potential target genes were identified by luciferase reporter and Western blot assays. The expression level of miR-141 in PDAC tissues was significantly lower than that in corresponding nontumorous tissues. Downregulation of miR-141 correlated with poorer pT and pN status, advanced clinical stage, and lymphatic invasion. Also, low miR-141 expression in PDAC tissues was significantly correlated with shorter overall survival, and multivariate analysis showed that miR-141 was an independent prognostic factor for PDAC patients. Further, functional researches suggested that miR-141 inhibits growth and colony formation, and enhances caspase-3-dependent apoptosis in PANC-1 cells by targeting Yes-associated protein-1 (YAP1). Therefore, miR-141 is an independent prognostic factor for PDAC patients, and functions as a tumor suppressor gene by targeting YAP1.

Role of miR-124 and miR-141 in the regulation of vascular reactivity and the relationship to RhoA and Rac1 after hemorrhage and hypoxia

“…Studies have shown that expressions of miR-23 and miR-27 were upregulated during the normal development of retinal blood vessels and in response to laser-induced choroidal neovascularization (31). Clusters of miR-143/miR-145 are located in VSMCs, and deletion of these clusters can affect VSMC contractility and blood pressure (7,25).…”

“…Abnormal expression of various miRNAs has been observed in the regulation of vascular function (1,31). For example, miR-145 participates in the regulation of VSMC contractility, and removal of miR-145 reduces the increase in systolic pressure in response to angiotensin II (1).…”

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

“…Emerging evidence suggested that specific miRNA profiles were capable of distinguishing malignant and non-malignant tissues [128], raising the feasibility of miRNAs in early detection of cancer, prognosis informing, and treatment response monitoring. It was reported that the expression level of miR-141 in PDAC tissues was significantly lower than that in corresponding nontumorous tissues [90]. Downregulation of miR-141 correlated with poorer pT and pN status, advanced clinical stage, lymphatic invasion, and shorter overall survival, suggesting that miR-141 was an independent prognostic factor for PDAC patients.…”

“…More importantly, overexpression of YAP1 could rescue not only the downregulation of YAP1 but also the growth inhibition and caspase-3-dependent apoptosis enhancement in PANC-1 cells induced by miR-141 upregulation [90]. YAP1 was first identified by virtue of its ability to associate with the SH3 domain of Yes-and Srcprotein-tyrosine kinases [91].…”

microRNAs with prognostic significance in pancreatic ductal adenocarcinoma: A meta-analysis

“…Title and abstract assessment identified 37 manuscripts appropriate for evaluation of prognostic miRNA biomarkers in PDAC and full text articles were obtained for these. On careful review of study methodologies, 19 reports were excluded (Additional file 1: Table S1), of which 13 were studies focusing on a miRNA not investigated by a second study and therefore a pooled analysis would not be possible [19][20][21][22][23][24][25][26][27][28][29][30][31]. The details for the other 6 excluded studies can be seen in Additional file 2: Supplementary Results.…”