LncRNA HMGA1P4在肝细胞癌中的表达及其与miR-4436a调控关系的研究

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摘要目的：探讨长链非编码RNA（lncRNA）高迁移率族蛋白A1假基因4（ high mobility group A1pseudogene 4，HMGA1P4）在肝细胞癌（hepatocellular carcinoma，HCC）组织中的表达及临床意义，并验证HMGA1P4与miR4436a的调控机制及其对肝细胞癌细胞株迁移和侵袭能力的影响。方法：采用实时荧光定量PCR检测肝细胞癌组织芯片中HMGA1P4和miR-4436a的表达；分析肝细胞癌组织中HMGA1P4的相对表达量与患者临床病理参数及预后的关系；通过Transwell实验验证HMGA1P4与miR4436a对肝细胞癌细胞株HepG2迁移和侵袭能力的影响；采用双荧光素酶报告实验验证HMGA1P4与miR-4436a之间的调控关系。结果： HMGA1P4在肝细胞癌组织中异常高表达，而miR4436a在肝细胞癌组织中的表达下调；在肝细胞癌组织中HMGA1P4的异常高表达与肿瘤淋巴结转移，TNM分期，复发，血清γ谷氨酰转肽酶（γ-GGT）水平，细胞程序性死亡配体1（PD-L1）、表皮生长因子受体（EGFR）以及细胞毒T淋巴细胞抗原4（CTLA-4）状态相关；在TNM Ⅰ～Ⅳ期、TNM Ⅰ期、TNM Ⅱ期的肝细胞癌患者中，HMGA1P4高表达组患者总体生存率和无复发生存率较低表达组患者显著降低；HMGA1P4高表达是肝细胞癌患者预后较差的独立危险因素。Transwell实验表明下调miR4436a能够逆转HMGA1P4沉默对HepG2细胞迁移和侵袭的抑制作用；双荧光素酶报告实验表明HMGA1P4能够调控miR4436a。结论：HMGA1P4的异常高表达对肝细胞癌恶性生物学行为以及不良预后起到促进作用，其能够通过调控miR4436a 促进肝细胞癌细胞的迁移和侵袭。

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关键词 ：肝细胞癌, 长链非编码RNA, HMGA1P4, 迁移, 侵袭, miR-4436a

Abstract：［Abstract］Objective： To investigate the expression and clinical significance of long non-coding RNA (lncRNA) HMGA1P4 in hepatocellular carcinoma (HCC) tissues, and verify the regulatory mechanism of HMGA1P4 and miR4436a and its influence on the migration and invasion ability of hepatocellular carcinoma cell line. Methods： qRT-PCR was utilized to detect the expression of HMGA1P4 and miR4436a in hepatocellular carcinoma tissue microarrays; the correlation between HMGA1P4 expression in hepatocellular carcinoma tissues and the clinical pathological parameters or prognosis of patients was analyzed; the influence of HMGA1P4 and miR-4436a on the migration and invasion ability of the HepG2 cell line was verified by the transwell experiment; the regulatory relationship between HMGA1P4 and miR-4436a was verified by the dual luciferase report experiment.Results： HMGA1P4 was abnormally highly expressed in hepatocellular carcinoma tissues,whereas the expression of miR4436a was downregulated in hepatocellular carcinoma tissues; the abnormally high expression of HMGA1P4 was associated with lymph node metastasis, TNM staging, recurrence, serum γ-GGT levels, PD-L1, EGFR and CTLA-4 status, and among TNM Ⅰ-Ⅳ, TNM Ⅰ, TNM Ⅱ staging hepatocellular carcinoma patients, the overall survival rate and recurrence-free survival of hepatocellular carcinoma patients with high HMGA1P4 expression was significantly lower than low expression group. The high expression of HMGA1P4 was an independent risk factor for the poor prognosis of hepatocellular carcinoma patients.Transwell experiment revealed that downregulation of miR-4436a could reverse the inhibitory effect of HMGA1P4 silencing-mediated hepatocellular carcinoma cell migration and invasion,the dual luciferase report experiment showed that HMGA1P4 could regulate miR-4436a.Conclusion：The abnormally high expression of HMGA1P4 promotes the malignant biological behavior and poor prognosis of hepatocellular carcinoma. HMGA1P4 can promote the migration and invasion of hepatocellular carcinoma cells by regulating miR-4436a.

收稿日期: 2022-01-07

通讯作者: 石键（通讯作者），副主任技师，E-mail:shijianjyk@163.com

作者简介: 张云（1988—），女，主管技师，硕士

引用本文:

张云，石键. LncRNA HMGA1P4在肝细胞癌中的表达及其与miR-4436a调控关系的研究[J]. 江苏大学学报:医学版, 2022, 22(04): 338-344. ZHANG Yun,SHI Jian. Expression of lncRNA HMGA1P4 in hepatocellular carcinoma and its correlation with the regulation of miR-4436a. Journal of Jiangsu University(Medicine Edition), 2022, 22(04): 338-344.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2022/V22/I04/338

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