目的：探讨长链非编码RNA（long non-coding RNA, lncRNA）SNHG5在缺氧诱导肝细胞癌（hepatocellular carcinoma,HCC）细胞侵袭及迁移中的作用。方法：收集2017年1月至2018年6月西安交通大学第一附属医院手术切除的20例HCC患者的癌与癌旁组织标本，以及人HCC细胞系HepG2、MHCC-97L、MHCC-97H、Huh7和永生化人肝细胞LO2。利用生物信息学方法分析缺氧诱导因子1α（hypoxia-inducible factor 1α，HIF-1α）与SNHG5的结合位点，将pCMV-HIF-1α、shRNA-SNHG5（sh-SNHG5）质粒转染进HCC细胞，用qPCR法检测HCC组织和缺氧条件下HCC细胞中SNHG5的表达水平，用Western botting检测HCC细胞中HIF-1α蛋白的表达水平，用Transwell小室法检测沉默SNHG5后常氧和缺氧条件下对HCC细胞侵袭及迁移能力的影响。结果：分别与癌旁组织和LO2细胞比较，HCC组织和各细胞系中SNHG5表达水平显著上调（均P<0.01）。缺氧可上调HCC细胞中SNHG5的表达水平，其机制可能与缺氧活化HIF-1α 与 SNHG5 启动子结合从而促进其转录有关 ；缺氧能够增强 HepG2和 MHCC-97L 细胞的侵袭及迁移能力（均P<0.01），沉默SNHG5表达能够显著抑制缺氧条件下HepG2和MHCC-97L细胞的侵袭及迁移能力（均 P<0.01）。结论：SNHG5在HCC组织及细胞系中高表达，并在缺氧诱导的HCC细胞侵袭及迁移中发挥重要作用。

Objective: To explore the regulatory effect of long non-coding RNA (lncRNA) SNHG5 on invasion and migration of hypoxia-induced hepatocellular carcinoma (HCC) cells. Methods: A total of 20 pairs of cancer and para-cancerous tissue specimens resected from HCC patients in the First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to June 2018, and human HCC cell lines (HepG2, MHCC-97L, MHCC-97H , Huh7) as well as immortalized human liver LO2 cells were collected for this study.Bioinformatics methods were used to analyze the binding sites between hypoxia-inducible factor 1α (HIF-1α) and SNHG5. pCMVHIF-1α and shRNA-SNHG5 (sh-SNHG5) plasmids were transfected into HCC cells, respectively. qPCR was used to detect the expres‐sion level of SNHG5 in HCC tissues and hypoxia-induced HCC cells. Western botting was used to detect the expression level of HIF-1α protein in HCC cells, and Transwell chamber method was used to detect the migration and invasion ability of HCC cells after SNHG5 si‐lence under normoxia and hypoxia condition. Results: Compared with para-cancerous tissues and immortalized human liver LO2 cells,the expression of SNHG5 was significantly up-regulated in HCC tissues and cell lines (all P<0.01). Hypoxia promoted the expression level of SNHG5 in HCC cells, and its mechanism might be related to the combination of hypoxia-activated HIF-1α and SNHG5 promoter to promote its transcription. Hypoxia promoted the invasion and migration ability of HepG2 and MHCC-97L cells (all P<0.01), but knockdown of SNHG5 significantly inhibited the invasion and migration ability of HepG2 and MHCC-97L cells under hy‐poxic conditions (all P<0.01). Conclusion: SNHG5 is highly expressed in HCC tissues and cell lines and plays an important role in the invasion and migration of HCC cells induced by hypoxia.

陕西省重点研发计划资助项目（No. 2017ZDXM-SF-065）