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Int. J. Mol. Sci. 2017, 18(1), 78; doi:10.3390/ijms18010078

Genome-Wide Screen of miRNAs and Targeting mRNAs Reveals the Negatively Regulatory Effect of miR-130b-3p on PTEN by PI3K and Integrin β1 Signaling Pathways in Bladder Carcinoma

Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China
The First Clinical College, Chongqing Medical University, Chongqing 400016, China
College of Clinical Medicine, Southwest Medical University, Luzhou 646000, China
Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China
Author to whom correspondence should be addressed.
Academic Editors: Anthony Lemarié and Sylvie Monferran
Received: 20 November 2016 / Revised: 17 December 2016 / Accepted: 28 December 2016 / Published: 31 December 2016
(This article belongs to the Special Issue Integrins in Cancer)
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miRNAs have emerged as promising markers for tumors. However, the underlying mechanism of specific miRNAs in bladder cancer (BC) remains largely unknown. Here, a comprehensive miRNA/mRNA expression profile was executed by microarray assay for four pairs of bladder carcinoma and para-carcinoma tissues from patients with grade 2 (G2) T2. A total of 99 miRNAs and 4416 mRNAs were discovered to be significantly differentially expressed in BC tissues compared with controls. Five microRNAs and two mRNAs were validated by qRT-PCR in 30 pairs of samples, including G1–G3/T1–T4. Subsequently, we constructed a network with the five miRNAs-target mRNAs; gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were utilized to recognize the functions and associated pathways. Moreover, we further found that miR-130b-3p was significantly up-regulated and negatively correlated with phosphatase and tensin homolog (PTEN) expression in bladder cancer tissues. Next, we demonstrated that miR-130b-3p might target PTEN through bioinformatics and dual-luciferase reporter assay. Finally, we showed that miR-130b-3p could down-regulate PTEN expression, which promoted proliferation, migration, invasion and rearranged cytoskeleton through the activation of the PI3K and integrin β1 signaling pathway in bladder cancer cells. Inversely, miR-130b-3p inhibitors induced apoptosis. Taken together, this research investigated, for the first time, miR-130b-3p by an incorporated analysis of microRNA/mRNA expressions of a genome-wide screen in BC. Our findings suggest that the miR-130b-3p/PTEN/integrin β1 axis could play a critical role in the progression and development of BC and that miR-130b-3p might be a valuable clinical marker and therapeutical target for BC patients. View Full-Text
Keywords: miRNA; integrin β1; miR-130b; PTEN; invasion; bladder cancer miRNA; integrin β1; miR-130b; PTEN; invasion; bladder cancer

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Lv, M.; Zhong, Z.; Chi, H.; Huang, M.; Jiang, R.; Chen, J. Genome-Wide Screen of miRNAs and Targeting mRNAs Reveals the Negatively Regulatory Effect of miR-130b-3p on PTEN by PI3K and Integrin β1 Signaling Pathways in Bladder Carcinoma. Int. J. Mol. Sci. 2017, 18, 78.

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