title: 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.
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.
authors.affiliation: Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China. 15123824592@163.com.
authors.forename: Mengxin
authors.initials: M
authors.lastname: Lv
authors.affiliation: The First Clinical College, Chongqing Medical University, Chongqing 400016, China. mylifeemail@163.com.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China. 15310432691@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Chi
authors.affiliation: College of Clinical Medicine, Southwest Medical University, Luzhou 646000, China. 18983004784@163.com.
authors.forename: Mengge
authors.initials: M
authors.lastname: Huang
authors.affiliation: Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. 13150535015@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China. chjunxia@cqmu.edu.cn.
authors.forename: Junxia
authors.initials: J
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D019012:Integrin beta1; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: PTEN; bladder cancer; integrin β1; invasion; miR-130b; miRNA