MiR-373-3p促进肺腺癌细胞的侵袭转移  

MiR-373-3p Promotes Invasion and Metastasis of Lung Adenocarcinoma Cells

作　　者：吴爱兵[1] 李金媚[1] 吴昆鹏[1] 莫艳丽[1] 罗怡平[1] 叶海茵 沈湘[1] 李姝君[1] 梁亚海[1] 刘美莲[1] 杨志雄[1] 

机构地区：[1]广东医学院附属医院肿瘤科,湛江524000

出　　处：《中国肺癌杂志》2015年第7期427-435,共9页Chinese Journal of Lung Cancer

基　　金：国家自然基金项目(No.81201672);广东省省级科技计划项目(No.2013B021800078;No.kz1153);广东医学院博士研究启动基金项目(No.B2012032)资助~~

摘　　要：背景与目的肺癌位居全球癌症相关死亡率的首位,其中肿瘤转移是导致肺癌患者死亡的主要原因,研究表明mi R-373与多种肿瘤细胞的侵袭转移有密切关系。本研究旨在探讨mi R-373-3p在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达情况及其对肺腺癌细胞侵袭转移能力的影响。方法利用q RTPCR法检测mi R-373-3p在NSCLC组织和肺腺癌细胞株中的表达。瞬时转染hsa-mi R-373-3p的mimics和inhibitor至肺腺癌H1299和A549细胞株中,利用Transwell小室检测转染后肺腺癌细胞侵袭转移能力的改变,Western blot检测转染后肺腺癌细胞中基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)及MMP-14蛋白水平的改变。结果mi R-373-3p在51例NSCLC组织和5种肺腺癌细胞株中均明显高表达。在mi R-373-3p低表达的H1299细胞中过表达mi R-373-3p,细胞的侵袭转移能力明显提高,同时MMP-9及MMP-14的表达上调;在mi R-373-3p高表达的A549细胞中抑制mi R-373-3p表达,细胞的侵袭转移能力下降,并且下调MMP-9和MMP-14的表达。结论 mi R-373-3p可能通过正向调节MMP-9、MMP-14的表达而促进肺腺癌细胞的侵袭转移能力。Background and objective Lung cancer is the leading cause of cancer-related deaths worldwide, and metastasis is the major cause of death in lung cancer patients. MiR-373 is closely associated with invasion and metastasis in other tumor cells. This study explored the expression of miR-373-3p in non-small cell lung cancer （NSCLC） and its effect on the invasive and metastatic capabilities of lung adenocarcinoma cells, as well as their mechanisms of action. Methods The expression ofmiR-373-3p in NSCLC tissues and lung adenocarcinoma cell lines was detected by quantitative reverse transcription polymerase chain reaction. The roles of miR-373-3p in regulating lung adenocarcinoma cell invasion and metastatic properties were analyzed with miR-373-3p mimic/inhibitor-transfected cells via Transwell chamber assay. Matrixmetalloproteinase MMP-9 and MMP-14 protein levels were detected by Western blot in lung cancer calls after transfection. Results MiR-373- 3p was upregulated in 51 NSCLC tissues and 5 NSCLC cell lines. Gain-of-function and loss-of-function studies showed that overexpression of miR-373-3p promoted H1299 cell migration and invasion, which resulted in upregulation of MMP-9 and MMP-14. By contrast, miR-373-3p knockdown inhibited these processes in A549 cells and downregulated the expression of MMP-9 and MMP-14. Conclusion Our results demonstrated that miR-373-3p participated in the invasion and metastasis of lung adenocarcinoma cells, partly by upregulation of MMP-9 and MMP-14.

关 键 词：肺肿瘤 MiR-373 MMP 9 MMP-14 侵袭 转移 

分 类 号：R734.2[医药卫生—肿瘤]