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


ABSTRACT: Background: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-?/smad pathway by binding to GREM1. Methods: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-?/smad pathway was subsequently blocked with si-TGF-? to investigate its involvement. Results: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-?/smad pathway by binding to GREM1. The silencing of TGF-?1 was shown to reverse the effects induced by downregulated expression of miR-137. Conclusions:This study suggests that upregulated miR-137 suppresses the tumor progression in CC via blocking the TGF-?/smad pathway by binding to and negatively regulating GREM1.

SUBMITTER: Miao H 

PROVIDER: S-EPMC6533679 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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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.

Miao Hui H   Wang Nuan N   Shi Lin-Xin LX   Wang Zheng Z   Song Wen-Bo WB  

Cancer cell international 20190523


<h4>Background</h4>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.<h4>Methods</h4>Microarray analysis was initially adopted to predict the differentially expressed genes and the miRNAs related to CC,  ...[more]

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