miR-143在人膀胱癌细胞中的作用及机制

目的：microRNAs（miRNAs）的异常表达与多种疾病密切相关，并有可能用于肿瘤治疗。本研究探讨了miR一143在人膀胱癌细胞中的作用及机制，为膀胱癌的临床诊治提供参考。方法：采用体外培养的T24细胞株为研究对象，按照处理方式分为空白对照组（T24）、阴性对照组（NC）、miRNA-143转染组（miR-143）以及si—COX-2转染组（si—COX-2）。3H—thymidine法和Transwell趋化实验检测T24细胞增殖和迁移能力，免疫印迹法检测COX一2蛋白表达变化。结果：miR-143和si—COX-2转染T24细胞48h-72h后，细胞增值能力较正常T24细胞相比下降36％．49％（P〈0．01），迁移能力下降81％。免疫印迹结果表明，si—COX-2或miR-143转染的T24细胞内源性COX-．2表达水平显著减少至正常T24细胞表达水平的O．39和0-31倍（P〈0．01）。结论：miR-143可降低膀胱癌T24细胞增值力和侵袭力，并抑制COX．2表达。miR-143可能通过COX-2通路发挥对膀胱癌T24细胞的增殖和侵袭的抑制作用。研究结果更加明确了microRNA在癌症中的功能，提示miR-143可作为膀胱癌的治疗候选药物。本研究为探索肿瘤生物标志物和治疗提供新的启示。

Role of miR-143 in Bladder Carcinoma and Underlying Mechanisms

Objective： Aberrant expression ofmicroRNAs （miRNAs） is implicated in numerous disease states and miRNAs have the potential to be used for cancer therapeutics. The present study is to determine the role of miR-143 in bladder carcinoma and underly- ing mechanisms and provide the reference for clinical diagnosis and treatment of bladder cancer. Methods： According to the different treatments, T24 cells were divided into normal control group （ T24 ）, negative control group （NC）, miR- 143 transfection group （ miR- 143 ） and si-COX-2 transfection group （si-COX-2）. The activities of proliferation and migration was examined by 3H-thymidine and Transwell chemotaxis assay respectively. The expression level of COX-2 was determined by Western blotting. Results： Restoration of miR-143 and si-COX-2 by cell transfection in T24 cancer cells led to decreased proliferation and mobility by 36%-49% when transfected for 48h and 72h. lmmunohistochemical results showed that compared with normal control, the expression of COX-2 in miR-143-transfected T24 cells was decreased significantly （P〈0.01）. Conclusion： miR-143 by cell transfection in T24 cancer cells can reduce proliferation and mobility and decrease COX-2 expression, which demonstrates that the role ofmiR-143 in the proliferation and migration of the cancer cells is due to the involvement ofmiR-143 in COX-2 pathway. Our findings will help to further understand the functions of miRNAs in cancer cells and point to a specific potential of miR-143 may be employed as a therapeutic agent for bladder carcinoma. The results provide insights into the development of novel tumor markers or new therapeutic strategies.