Yang Cheng, Sun Junjun, Liu Weifeng, Yang Yanhui, Chu Zhijie, Yang Tianbao, Gui Yang, Wang Du
Department of Hepatobiliary, Henan University of Science and Technology First Affiliated Hospital Luoyang 471000, Henan Province, China.
Am J Transl Res. 2019 Feb 15;11(2):953-963. eCollection 2019.
Long noncoding RNAs (lncRNAs) play key roles in various malignancy pathogenesis. However, the mechanisms remain poorly understood in the development and progression of colorectal cancer (CRC). Here, we focused on the specific role of human leukocyte antigen (HLA) Complex P5 (HCP5) in CRC. Quantitative real-time PCR (qRT-PCR) analysis and western blot were used to assess the expression of HCP5 in CRC tissues. The association between the expressions of HCP5 and miR-139-5p was assessed by Pearson's correlation analysis. The prognosis of CRC patients was analyzed by Kaplan-Meier survival analysis. Specific siRNAs were stably transfected into CRC cells with lentivirus approaches. The proliferative, migrative and invasive capacities of CRC cells were detected by Transwell, MTT and scratch assay, respectively. Dual-luciferase assay was performed to measure miR-139-5p-targeted relationship with lncRNA HCP5. HCP5 overexpression and of miR-139-5p downregulation were dramatically correlated with low TNM stage, poor differentiation, low tumor depth invasion in CRC patients (P < 0.05). Besides, HCP5 overexpression or ZEB1 knockdown repressed Snail family transcriptional repressor (SNAI) and vimentin expressions, upregulated E-cadherin expression, and inhibited cell proliferation and metastasis (P < 0.05). Moreover, luciferase reporter assay demonstrated that miR-139-5p was a directly target of HCP5 (P < 0.05). Overall, the present study indicated that HCP5 played a key regulator in CRC development and progression by targeting HCP5/miR-139-5p/ZEB1 axis, which may serve as a novel therapeutic target for CRC therapy.
长链非编码RNA（lncRNAs）在多种恶性肿瘤的发病机制中发挥关键作用。然而，在结直肠癌（CRC）的发生和发展过程中，其机制仍知之甚少。在此，我们聚焦于人类白细胞抗原（HLA）复合体P5（HCP5）在CRC中的具体作用。采用定量实时聚合酶链反应（qRT-PCR）分析和蛋白质印迹法评估HCP5在CRC组织中的表达。通过Pearson相关性分析评估HCP5与miR-139-5p表达之间的关联。采用Kaplan-Meier生存分析法分析CRC患者的预后。利用慢病毒方法将特异性小干扰RNA（siRNAs）稳定转染至CRC细胞中。分别通过Transwell、MTT和划痕试验检测CRC细胞的增殖、迁移和侵袭能力。进行双荧光素酶试验以测定miR-139-5p与lncRNA HCP5的靶向关系。HCP5过表达和miR-139-5p下调与CRC患者的低TNM分期、低分化及肿瘤深度浸润密切相关（P<0.05）。此外，HCP5过表达或锌指蛋白E盒结合因子1（ZEB1）敲低可抑制Snail家族转录抑制因子（SNAI）和波形蛋白的表达，上调E-钙黏蛋白的表达，并抑制细胞增殖和转移（P<0.05）。此外，荧光素酶报告基因试验表明miR-139-5p是HCP5的直接靶点（P<0.05）。总体而言，本研究表明HCP5通过靶向HCP5/miR-139-5p/ZEB1轴在CRC的发生和发展中起关键调节作用，这可能为CRC治疗提供一个新的治疗靶点。
