MicroRNA-190b expression predicts a good prognosis and attenuates the malignant progression of pancreatic cancer by targeting MEF2C and TCF4

Abstract

MicroRNAs (miRNAs/miRs) are key components of regulatory networks in cancer. Although miR-190b is an impor- tant tumor-related miRNA, its role in pancreatic cancer has not been extensively investigated. The aim of the present study was to examine the expression of miR-190b in pancreatic cancer cell lines and tissues and evaluate its effects on cancer progression. Reverse transcription-quantitative PCR (RT-qPCR) analysis was used to measure miR-190b expression levels in human pancreatic cancer cell lines and tissues, and the association between miR-190b expression and clinicopathological charac- teristics was assessed. An in vitro Transwell invasion assay and an in vivo metastasis formation assay were performed using pancreatic cancer cells. The effect of miR-190b on pancreatic cancer cell proliferation was evaluated using a Cell Counting Kit-8 assay based on an in vivo xenograft mouse model. The direct targets of miR-190b were predicted using bioinformatics tools and were validated through western blotting and lucif- erase reporter assays. Pancreatic cancer cell lines and tissues were found to express lower levels of miR-190b compared with normal cells and adjacent non-tumor tissues. Furthermore, high expression of miR-190b was found to be positively correlated with low T, N and American Joint Committee on Cancer classi- fications, and predicted a good prognosis. miR-190b was shown to exert suppressive effects on cancer cell proliferation, invasion and metastasis. In addition, it was also found that miR-190b directly targeted myocyte enhancer factor 2C (MEF2C) and transcription factor 4 (TCF4) in pancreatic cancer, thus serving as a tumor suppressor and a predictor of good prognosis in pancreatic cancer. The immunohistochemistry and RT-qPCR results indicated that the MEF2C and TCF4 expression levels were negatively correlated with the miR-190b expression levels. The findings of the present study highlight the value of miR-190b as a novel target candidate for pancreatic cancer diagnosis and therapy.