Expression of long non-coding RNA UCA1 and miR-34b in bladder cancer and analysis of clinic-pathologic correlation

Abstract

Objective To study the expression of long non-coding RNA (lncRNA)- urothelial carcinoma associated 1(UCA1) and miR-34b in bladder cancer and its correlation to the clinicopathologic features of bladder cancer. Methods Between January 2011 and October 2012 , the expression of UCA1 and miR-34b in 5 bladder cancer cell lines (T24, BIU-87, EJ, T24-MMC, T24-ADM)and 1 normal bladder cell lines (SV-HUC-1) were measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). Meanwhile, the 56 bladder cancer specimens and paraneoplastic normal bladder tissues, which diagnosed by pathology were collected from bladder cancer patients undergoing radical resection of bladder. Among them, 41 cases were male and 15 cases were female. The mean age was (68.4±7.5)years old, range 52 to 78 years.43 cases were older than 65 years old, and 13 cases were less than 65 years old. The pathological classification included non muscle-invasive bladder cancer (NMIBC) 18 cases, muscle-invasive bladder cancer 38 cases; low grade papillary urothelial carcinoma 22 cases, high grade papillary urothelial carcinoma 34 cases; 12 cases were primary lesion, the other 44 cases were diagnosed as tumor recurrence. Real-time RT-PCR was performed to analyze the expression of UCA1 and miR-34b. Results The relative expression levels of UCA1 in the normal bladder cell lines (SV-HUC-1) and 5 bladder cancer cell lines (T24, BIU-87, EJ, T24-MMC and T24-ADM)were (0.0675±0.0133), (0.2934±0.0531), (0.4246±0.0650), (0.4206±0.0826), (0.6472±0.0875) and (0.7165±0.1032), respectively (P<0.05). Moreover, the expression levels of UCA1 were up-regulated in 2 drug resistant bladder cancer cells lines T24-MMC(0.6472±0.0875)and T24-ADM(0.7165±0.1032), as compared with the T24 bladder cancer lines (0.2934±0.0531) , respectively (P<0.05). However, the expression levels of miR-34b in 5 bladder cancer cell lines [T24(0.1600±0.0455), BIU-87(0.1720±0.0658), EJ(0.1150±0.0352), T24-MMC(0.0576±0.0087), T24-ADM(0.0510±0.0125)]were decreased(P<0.05), as compared with normal bladder cell lines SV-HUC-1(0.6384±0.1083). Moreover, the expression levels of miR-34b were down-regulated in 2 drug resistant bladder cancer cells lines T24-MMC(0.0576±0.0087)and T24-ADM(0.0510±0.0125), as compared with the T24 bladder cancer lines T24(0.1600±0.0455), respectively (P<0.05). The relative expression levels of UCA1 and miR-34b in bladder cancer tissues and paraneoplastic normal bladder tissues were (0.4225±0.0714)vs.(0.0532±0.0192)and(0.0340±0.0134)vs.(0.5643±0.0616), respectively (P<0.05). Statistical correlation analysis showed that UCA1 to be significantly negative correlated with miR-34b in bladder cancer specimens(r=-0.54, P<0.05). The high level of UCA1 and low level of miR-34b were significantly correlated with tumor malignant grade, invasiveness and recurrence. The 3-year overall survival rate (OS) in UCA1(+ )/miR-34b(-) group (27.6%) were significantly worse compared with non UCA1(+ )/miR-34b(-) group(73.7%). Conclusion High expression of UCA1 and low expression of miR-34b were associated with the occurrence and development of bladder cancer. Key words: Urinary bladder neoplasms; Long non-coding RNA; Urothelial carcinoma associated 1; MicoRNAs