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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

1
Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China
2
The First Clinical College, Chongqing Medical University, Chongqing 400016, China
3
College of Clinical Medicine, Southwest Medical University, Luzhou 646000, China
4
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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Abstract

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
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MDPI and ACS Style

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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