Role Of MiR-26 Mediated Gene HMGA1 In Bladder Cancer

Bladder cancer(BC), as the 2nd most common malignancy of the urinary tract, has an increased morbidity and mortality worldwidely. Especially, it is the 8th most common malignant tumor in males and the 12 th in females in China. Even now, the pathogenesis, diagnosis, therpy about BC have not been known clearly. It is believed that various factors would be involved in tumorigenesis and progression of bladder cancer. MicroRNAs(mi RNAs), which are a group of single strand, endogenous, non-coding RNA molecules, play a great role at the post-transcriptional level by regulating target-gene expression. Most of the cancers, including bladder cancer, whose carcinogens expression were been down-regulating by micro RNAs and can be inhibited about tumorigenesis, progression, tumormetastasis.This study was aimed to discussing the mechanism of inhibition in bladder cancer by mi R-26 and its target gene HMGA1.Materials and methods:1. 126 urothelial bladder cancer patients were selected; By use of q RT-PCR, the expression of mi R-26 a and HMGA1 mRNA were detected respectively. The expression of mi R-26 a or HMGA1 in UBC tissues and corresponding non-cancerous tissues was analysed refering to the differences in categorical variables, patient survival.2. Using online algorithms to identify downstream targets of miR-26 a, bioinformatics analysis was carried out that the 3’-UTR of the HMGA1 mRNA contains a mi R-26a-com-plementary binding site. Further qPCR,Western Blot and luciferase assay were used to identify the relation between miR-26 and its target gene HMGA1.3. After transfected with mi R-26 mimic, the varieties of tumorigenesis, progression, tumormetastasis effect in bladder cancer were studied.Results :1. Of 126 UBC patients, 70 cases were low s expression of mi R-26 a and 68 were high expression of HMGA1 mRNA(both P < 0.001). The levels of expression of mi R-26 a in UBC tissues were significantly negatively correlated with those of HMGA1 mRNA(determined by Spearman’s correlation,r = –0.72, P < 0.001).2. The advanced pathological stage, high tumor grade, and positive lymph node metastasis were significantly interconnected with low expression levels of mi R-26 a or high expression levels of HMGA1 in UBC(all P < 0.05).3. A significant relationship was found between longer overall survival and low mi R-26 a expression or high HMGA1 expression respectively(both P < 0.001, log-rank test). So as to the disease-free survival. Those patients who were both low mi R-26 a expression and high HMGA1 expression had the poorest prognosis.4. the 3’-UTR of the HMGA1 m RNA was found containing a mi R-26a-complementary binding site, Thus, it was confirmed that HMGA1 was a potential key mediator of tumor suppression function of mi R-26 a in bladde5. All the q PCR, Western Blot and luciferase assay were used to identify the relation between mi R-26 and HMGA1. And then HMGA1 was revealed as a direct target of mi R-26.6. Transfected with miR-26 mimic and up-regulated expression of mi R-26, G1-phase arrest in T24 cells was induced. The cell viability, colony formation ability in vitro/in vivo were inhibited..Conclusion:By qPCR, miR-26 showwed down-regulation in bladder cancer, but HMGA1 showwed up-regulation. Further Western Blot and luciferase assay, miR-26, with its specific target-gene HMGA1, revealed an important anti-tumor role at bladder cancer cells.