Lv Mengxin, Zhong Zhenyu, Chi Hong, Huang Mengge, Jiang Rong, Chen Junxia
Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China.
The First Clinical College, Chongqing Medical University, Chongqing 400016, China.
Int J Mol Sci. 2016 Dec 31;18(1):78. doi: 10.3390/ijms18010078.
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.
微小RNA(miRNA)已成为有前景的肿瘤标志物。然而,特定miRNA在膀胱癌(BC)中的潜在机制仍 largely未知。在此,通过微阵列分析对4对来自2级(G2)T2期患者的膀胱癌组织和癌旁组织进行了全面的miRNA/mRNA表达谱分析。与对照相比,共发现99种miRNA和4416种mRNA在BC组织中显著差异表达。通过qRT-PCR在30对样本(包括G1-G3/T1-T4)中验证了5种microRNA和2种mRNA。随后,我们构建了一个包含这5种miRNA及其靶mRNA的网络;利用基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析来识别其功能和相关途径。此外,我们进一步发现miR-130b-3p在膀胱癌组织中显著上调,且与磷酸酶和张力蛋白同源物(PTEN)表达呈负相关。接下来,我们通过生物信息学和双荧光素酶报告基因检测证明miR-130b-3p可能靶向PTEN。最后,我们表明miR-130b-3p可下调PTEN表达,通过激活PI3K和整合素β1信号通路促进膀胱癌细胞的增殖、迁移、侵袭并重排细胞骨架。相反,miR-130b-3p抑制剂可诱导细胞凋亡。综上所述,本研究首次通过对BC全基因组范围内的miRNA/mRNA表达进行综合分析来研究miR-130b-3p。我们的研究结果表明,miR-130b-3p/PTEN/整合素β1轴可能在BC的进展和发展中起关键作用,且miR-130b-3p可能是BC患者有价值的临床标志物和治疗靶点。