Overexpression of mircoRNA-137 inhibits cervical cancer cell invasion, migration and epithelial-mesenchymal transition by suppressing the TGF-β/smad pathway via binding to GREM1

• Published in: Cancer cell international 2019-05, Vol.19 (1), p.147-147, Article 147
• Main Authors: Miao, Hui, Wang, Nuan, Shi, Lin-Xin, Wang, Zheng, Song, Wen-Bo
• Format: Article
• Language: English
• Subjects: Apoptosis; Binding sites; Bioinformatics; Breast cancer; Cell migration; Cell proliferation; Cervical cancer; Cervix; Colonies; Colorectal cancer; DNA microarrays; Epithelial–mesenchymal transition; Gene expression; GREM1; Growth factors; Gynecology; Immunoglobulins; Invasion; Laboratory animals; Mesenchyme; Mesothelioma; Metastasis; Mice; MicroRNA-137; MicroRNAs; miRNA; Obstetrics; Primary Research; Proteins; Reporter gene; Smad protein; TGF-β/smad pathway; Tissues; Transforming growth factor-b1; Tumorigenesis; Tumorigenicity; Womens health
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-019-0852-8

Accumulating evidence has highlighted the tumor suppressive roles of microRNA (miRNAs) in cervical cancer (CC). In the present study, we aim to delineate the functional relevance of microRNA-137 (miR-137) in influencing epithelial-mesenchymal transition (EMT), and other CC cell biological activities via the TGF-β/smad pathway by binding to GREM1. Microarray analysis was initially adopted to predict the differentially expressed genes and the miRNAs related to CC, followed by the measurement of the expression patterns of GREM1, EMT-related factors in the CC tissues and the adjacent tissues. Dual luciferase reporter gene assay was conducted to determine the relationship between miR-137 and GREM1. Gain-of- and loss-of-function experiments were conducted to characterize the effects of miR-137 and GREM1 on the colony formation, proliferation, apoptosis, migration, and invasion of CC cells in vitro, and the tumorigenicity of the CC cells in nude mice. The TGF-β/smad pathway was subsequently blocked with si-TGF-β to investigate its involvement. Reduced miR-137 expression and increased GREM1 expression were predicted in CC, which was subsequently observed in the CC tissues and cells. Notably, GREM1 was a target gene of miR-137. The overexpressed miR-137 was found to inhibit EMT, cell proliferation, colony formation, invasion, migration and tumorigenesis in nude mice. In addition, miR-137 was noted to inhibit the activation of the TGF-β/smad pathway by binding to GREM1. The silencing of TGF-β1 was shown to reverse the effects induced by downregulated expression of miR-137. This study suggests that upregulated miR-137 suppresses the tumor progression in CC via blocking the TGF-β/smad pathway by binding to and negatively regulating GREM1.