MicroRNA-34Gene Inhibits Growth Of Bladder Cancer Cell And The Mechanism Of Anti-tumor Effect Of Cisplatin

Objective:Recently studies have reported that miRNA participates in cell proliferation and differentiation, and can affect gene expression resulting from mRNA degradation or inhibit its translation, through mRNA-specific or non-specific pairing. MiRNA can also regulate cell proliferation and apoptosis in the process of tumorigenesis. MiRNA such as the most representative miR-34family highly related to the tumor suppressor protein p53. MiR-34can participate in the network path of tumors by regulating p53. In this paper, we chose low-miR-34expressed cancer cell T24as the research object, and explored the biological characteristics (proliferation, apoptosis and metastasis invasion) of bladder cancer after miR-34reconstruction with cisplatin, as well as the impact of tumor resistance. We also detected the gene and protein expression of Bcl-2, one of the miR-34potential target genes in bladder cancer T24cells after miR-34reconstruction, thus further elaborating the molecular mechanism.Methods:1We utilized quantitative PCR to detect the miR-34expression levels in different bladder cancer cell lines;2We constructed the miR-34mimic (miR-34analog fragment) and transferred it to low miR-34expressed bladder cancer T24cells; 3We used miR-34mimic combined with chemotherapy drug cisplatin in bladder cancer cells;4MTT, FCM and Traswell methods were used to detect cell proliferation, apoptosis and invasion;5Quantitative PCR was performed to detect the expression level of miR-34; WB and quantitative PCR were used to detect the expression level of Bcl-2; the activity of apoptosis-related protein caspase-3was determined by MTT.Results:1We successfully fulfilled the miR-34reconstruction in the low miR-34expressed bladder cancer cell line;2The miR-34reconstructed bladder cancer cells showed decreased capacity of proliferation, a rise in the proportion of apoptosis, as well as reduced capacity of invasion;3MiR-34is expected to enhance the antitumor effect of the anticancer drug cisplatin;4MiR-34could promote apoptosis of bladder cancer cells by regulating the expression of the apoptosis suppressor gene Bcl-2as well as caspase-3.Conclusion:Increased or decreased expression of miR-34could affect the proliferation and apoptosis of bladder cancer cells. MiR-34participated in the tumor suppression by p53protein, through regulating inhibitors of apoptosis Bcl-2and caspase-3. Moreover, miR-34in combination with cisplatin could improve the suppression of bladder cancer cells.