长链非编码RNA-HIT在膀胱癌组织的表达及其对膀胱癌细胞生物学的影响

Expression of the long non-coding RNA HIT in human bladder cancer tissues and its effect on bladder cancer cell biology

目的观察人膀胱移行细胞癌(BTCC)患者肿瘤组织及膀胱癌细胞株中长链非编码RNA(lncRNA)HIT的表达,探讨lncRNA-HIT对膀胱癌细胞的生物学影响。方法应用实时定量反转录聚合酶链反应(RT-qPCR)检测2016年9月至2019年3月华中科技大学同济医学院附属武汉中心医院54例BTCC患者手术切除的癌组织及其配对毗邻正常黏膜组织中lncRNA-HIT的表达水平;统计分析其表达水平与患者临床病理特征之间的相关性。采用短发卡RNA(shRNA)干扰lncRNA-HIT,观察其对膀胱癌细胞的凋亡、增殖及侵袭等生物学的影响。两组均数间比较用t检验,多组间均数比较采用单因素方差分析。结果BTCC患者癌组织中lncRNA-HIT的表达量较配对癌旁正常组织上调(t=5.763,P<0.05);lncRNA-HIT在膀胱癌细胞株EJ、UMUC3和T24细胞的表达较正常膀胱细胞系SV-HUC-1细胞明显上调(t=15.030、13.020、14.050,P<0.05)。lncRNA-HIT异常增高与患者肿瘤分级(χ^2=6.862,P<0.01)、分期(χ^2=14.814,P<0.01)、淋巴结转移(χ^2=9.429,P<0.01)、远处转移(χ^2=12.523,P<0.01)等密切相关,但与性别(χ^2=0.441,P>0.05)和年龄(χ^2=0.106,P>0.05)无明显相关,体外靶向干扰实验显示下调lncRNA-HIT可以显著促进膀胱癌细胞的凋亡,抑制膀胱癌细胞增殖和其侵袭能力。结论lncRNA-HIT在BTCC患者肿瘤组织中显著增高。

Objective To investigate the expression of long non-coding RNA(lncRNA)HIT in tumor tissues of bladder transitional cell cancer(BTCC)and its role in the biological behavior of cancerous cells.Methods The expression level of lncRNA-HIT in tumor tissues and adjacent non-tumor tissues of BTCC patients from surgically resected was detected by real-time quantitative polymerase chain reaction(Real-time PCR),and its correlation with clinicopathological characteristics was analyzed.The lncRNA-HIT was knocked down in UMUC3 and T24 cell lines to investigate its biological effects on apoptosis,proliferation and invasion of bladder cancer cells.Results The expression of lncRNA-HIT in tumor tissues of BTCC patients was significantly increased as compared with that in adjacent non-tumor tissues(t=5.763,P<0.05).The expression of lncRNA-HIT in bladder cancer cell lines EJ,UMUC3 and T24 was significantly higher than that in normal bladder cell lines SV-HUC-1(t=15.030,13.020,14.050,P<0.05).We also found that the high expression of lncRNA-HIT was significantly associated with tumor differentiation(G1 vs.G2+G3,χ^2=6.862,P<0.01),stage(Ta,T1 vs.T2-T4,χ^2=14.814,P<0.01),presence of lymph node metastasis(χ^2=9.429,P<0.01)and presence of distant metastasis(χ^2=12.523,P<0.01).However,no significant differences were observed in lncRNA-HIT expression among patients with different gender(male vs.female,χ^2=0.441,P>0.05)or age(≥55 years vs.<55 years,χ^2=0.106,P>0.05).Knockdown of lncRNA-HIT could promote the apoptosis capability,and inhibit the capability of proliferation and invasion of bladder cancer cells.Conclusion lncRNA-HIT is significantly highly expressed in tumor tissues of BTCC patients.