中国肿瘤生物治疗杂志2019，Vol.26Issue(4)：409-416,8.DOI:10.3872/j.issn.1007-385x.2019.04.007
lncRNA HCG18/miR-17-5p/HMGA2分子轴调控非小细胞肺癌细胞增殖及迁移
lncRNA HCG18 regulates the proliferation and metastasis of non-small cell lung cancer cells through targeting miR-17-5p/HMGA2 axis
摘要
Abstract
Objective: To investigate the mechanism of lncRNA HCG18/miR-17-5p/HMGA2 axis regulating the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells. Methods: Sixty-two pairs of NSCLC tissues and corresponding para-cancerous tissues collected at Central Hospital of Chengde City from June 2017 to June 2018 were used for this study; in addition, NSCLC cell lines (A549, NCI-H1299, H1650, NCI-H460) and human lung epithelial BEAS-B cells were also collected. mRNA expression levels of HCG18, miR-17-5p and high-mobility group AT-hook 2 (HMGA2) in NSCLC tissues and cell lines were measured by quantitative Real-time polymerase chain reaction (qPCR). Si-HCG18, miR-17-5p, miR-17-5p+HCG18 or pcDNA3.1-HMGA2 were transfected into A549 cells and NCI-H460 cells; CCK-8 assay was used to detect the proliferation of transfected cells, Transwell assay was used to detect the migration and invasion ability of cells, and Wb was used to analyze the expressions of HMGA2 and EMT associated proteins (E-cadherin, N-cadherin and vimentin). The target relationships between HCG18 and miR-17-5p, or between miR-17-5p and HMGA2 were confirmed by dual luciferase reporter gene assay. Mice A549 cell xenograft model with HCG18 knockdown was constructed, and the growth of transplanted tumor was observed. Results: lncRNA HCG18 was highly expressed in NSCLC tissues and cells (all P<0.01); HCG18 level was significantly increased in patients at late stage or with lymphnode metastasis; and high HCG18 level was correlated with poor prognosis and low survival rates of NSCLC patients (all P<0.01). Knockdown of HCG18 significantly inhibited NSCLC cell proliferation, migration and invasion (all P<0.01), up-regulated E-cadherin expression but suppressed N-cadherin and vimentin expression (all P<0.01), and the volume of xenograft was obviously decreased (P<0.05). Dual luciferase reporter gene assay confirmed the relationship between HCG18 and miR-17-5p as well as miR-17-5p and HMGA2. miR-17-5p transfection significantly inhibited NSCLC cell proliferation, migration and invasion (all P<0.01), and up-regulated E-cadherin expression, reversely suppressed N-cadherin and vimentin expression (all P<0.01); however, miR-17-5p + HCG18 transfection reversed the effect of miR-17-5p on NSCLC cells. Conclusion: HCG18 promotes the proliferation and migration of NSCLC cells through regulating miR-17-5p/HMGA2 axis.关键词
非小细胞肺癌/A549细胞/NCI-H460细胞/lncRNA HCG18/miR-17-5p/高迁移率族蛋白A2/增殖/迁移Key words
non-small cell lung cancer/A549 cell/CI-H460 cell/lncRNAHCG18/miR-17-5p/HMGA2/proliferation/migration分类
医药卫生引用本文复制引用
曲宝亮,穆怀博,勾建强,扬宇,马胜辉,杜春阳..lncRNA HCG18/miR-17-5p/HMGA2分子轴调控非小细胞肺癌细胞增殖及迁移[J].中国肿瘤生物治疗杂志,2019,26(4):409-416,8.基金项目
河北省科技计划资助项目(No.18277748D) （No.18277748D）
