| dc.description.abstract | Bladder cancer (BC) is a common malignant disease with poor prognosis in urinary system, which occurs in men more often than women and usually affects older adults. About 90% of bladder cancer is urothelial carcinoma (UC) which is known as transitional cell carcinoma (TCC) previously. UC is the most common urinary tract tumor in Taiwan patients. However, it is hard to be diagnosed at early stage. In addition, it has been found that the risk of developing UC in chronic kidney disease (CKD) patients is seven times higher than in normal people and the risk of developing UC in hemodialysis (HD) patients is 200-300 times higher than in normal people.
Our previous data showed that the expression of several miRNAs in urine and plasma were significant different between CKD patients and CKD patients with UC, or between HD patients and HD patients with UC. We chose these miRNAs as our candidate miRNAs to study their roles in BC.
Firstly, we analyzed the data of candidate miRNAs from ArrayExpress database and predicted the targets from four websites. Then, we obtained the survival rate curves of patients. The results showed that only the expression of miR-19b-1-5p significantly regulate survival of BC patients. Patients with high expression of miR-19b-1-5p had significantly longer overall survival than those with low expression. miR-19b-1-5p might act as a tumor suppressor. The expression of four miRNAs target genes significantly regulate survival of BC patients. Most interestingly, miR-19b-1-5p appeared to target EDN1 gene to have an impact on overall survival in BC patients.
Furthermore, we transfected negative control (NC) or candidate miRNA mimics in two BC cells (J82 and RT4) in order to know the function of these miRNAs in BC. We found that overexpression of candidate miRNAs could not significantly inhibit cell proliferation in J82 and RT4 cells. But, overexpression of miR-19a-5p and miR-155-5p could significantly decrease cell colonies in J82 cells. We also observed that overexpression of miR-150-5p could inhibit migration in J82 cells and overexpression of miR-19a-5p, miR-30a-5p, and miR-155-5p could inhibit invasion in J82 cells. The data indicated that these miRNAs might be associated with BC anti-carcinogenesis, but overexpression of miR-19b-1-5p did not inhibit cell proliferation, colony formation, migration and invasion.
Finally, because of different results from survival curves and functional tests, we investigated the expression of candidate miRNAs in patients’ serum and cells through GEO database and RT-qPCR analysis. We found that almost of candidate miRNAs have higher expression in BC. The data might indicate that UC-related miRNAs were involved in BC carcinogenesis, and we will further investigate the reasons for different results. | en_US |