长链非编码RNA XIST在胰腺癌中的表达及意义

目的:探讨长链非编码RNAXIST在胰腺癌组织中的表达及其作用。方法:实时定量PCR检测56对胰腺癌及癌旁正常胰腺组织标本中XIST的表达,以及XIST在人胰腺导管上皮细胞(HPDE)及7种胰腺癌细胞系(sPC-3、Bx PC-3、Capan-1、CFPAC-1、Hs766T、Panc-1、SW1990)中的表达,分析XIST表达与胰腺癌患者临床病理因素的关系;在XISTsi RNA干扰XIST高表达的胰腺癌细胞后,分别用MTT法和Brd U实验检测细胞的活力和增殖情况,Westernblot检测细胞中Ki-67、PCNA的蛋白的表达。结果:胰腺癌组织中XIST的表达量明显高于癌旁正常胰腺组织(2.452vs.0.9729,P0.001),且XIST高表达与胰腺癌患者的肿瘤分期(P=0.016)、淋巴结转移(P=0.032)有关。7种胰腺癌细胞系中XIST的表达量均明显高于HPDE细胞(均P0.05),其中SW1990细胞XIST表达量约为HPDE细胞的2.5倍。XISTsi RNA干扰SW1990细胞48h后,与未处理的SW1990细胞比较,细胞的活力(0.812vs.1.215)和增殖能力(0.708vs.1.007)均明显降低,Ki-67(0.467vs.1.027)与PCNA(0.600vs.0.997)的表达均明显下调(均P0.05)。结论:XIST在胰腺癌组织中表达升高,其高表达能促进胰腺癌细胞的生长,机制可能与其上调Ki-67、PCNA表达有关。

Expression of long non-coding RNA XIST in pancreatic cancer and its significance

Objective: To investigate the expression and action of long non-coding RNA XIST in pancreatic cancer tissue. Methods: The XIST expressions in specimens of 56 paired pancreatic cancer and adjacent normal pancreatic tissues as well as in normal human pancreatic duct epithelial cells (HPDE) and 7 different pancreatic cancer cell lines (sPC-3, BxPC-3, Capan-1, CFPAC-1, Hs766T, Panc-1 and SW1990) were examined by real-time quantitative PCR. The relations of XIST expression with the clinicopathologic factors of pancreatic cancer patients were analyzed; in pancreatic cancer cells with high XIST expression after interference by XIST siRNA, the viability and proliferation were detected by MTT and BrdU assay, and protein expressions of Ki-67 and PCNA were determined by Western blot analysis. Results: The XIST expression in pancreatic cancer tissue was significantly higher than that in adjacent normal pancreatic tissues (2.452 vs. 0.9729, P<0.001), and high XIST expression was significantly associated with tumor stage (P=0.016) and lymph node metastasis (P=0.032) of the patients. The XIST expression levels in all 7 types of pancreatic cell lines were significantly higher than that in HPDE cells (all P<0.05), in which, XIST expression level was about 2.5-fold higher in SW1990 cells than that in HPDE cells. In SW1990 cells after XIST siRNA interference for 48 h compared with untreated SW1990 cells, the viability (0.812 vs. 1.215) and proliferation ability (0.708 vs. 1.007) were significantly reduced, and protein expressions of Ki-67 ((0.467 vs. 1.027) ) and PCNA (0.600 vs. 0.997) were significantly down-regulated (all P<0.05). Conclusion: XIST expression is increased in pancreatic cancer tissue and its overexpression can promote the growth of pancreatic cancer cells, and the mechanism may be associated with its regulating Ki-67 and PCNA expressions.