Bi Xianxia, Wang Luwei, Li Hua, Ma Ying, Guo Ruoyu, Yue Jicheng, Kong Lijun, Gong Xiangqian, Jiao Fei, Chinn Eugene, Hu Jinxia
Peninsula Cancer Research Center of Binzhou Medical University, YanTai, Shandong 264003, P.R. China.
Yantai Environmental Sanitation Management Center, YanTai, Shandong 264000, P.R. China.
J Cancer. 2024 Mar 17;15(9):2746-2758. doi: 10.7150/jca.89733. eCollection 2024.
To explore the effects of miR-383-5p and serine hydroxymethyltransferase 2 (SHMT2) on the proliferation and migration of lung adenocarcinoma cells. SHMT2 expression in lung adenocarcinoma and normal tissues was investigated using The Cancer Genome Atlas database. Immunohistochemical analysis was performed to confirm SHMT2 expression in lung adenocarcinoma and adjacent normal lung tissues. Bioinformatics analysis and luciferase reporter assays were used to analyze the relationship between miR-383-5p and SHMT2 expression. The protein expression levels of SHMT2, vimentin, N-cadherin, E-cadherin, Bcl-2, and cyclinD1 were analyzed using western blotting. The reverse transcription-quantitative polymerase chain reaction was used to detect SHMT2 knockdown efficiency, miR-383-5p overexpression, and inhibition efficiency. The proliferative ability of cells was detected using the Cell Counting Kit-8 assay. The Transwell assay was used to detect the migration ability of cells. SHMT2 expression was significantly increased in patients with lung adenocarcinoma compared to that in control patients; the higher the SHMT2 expression the worse the outcomes were in patients with lung adenocarcinoma. SHMT2 knockdown inhibited the proliferation, migration, and epithelial-mesenchymal transition of lung adenocarcinoma A549 and H1299 cells. MiR-383-5p directly targeted and downregulated SHMT2 in A549 and H1299 cells. The effects of miRNA-383-5p on the proliferation and migration of these cells differed from those of SHMT2. Exogenous overexpression of SHMT2 reversed the miR-383-5p-induced proliferation and migration inhibition in A549 and H1299 cells. MiR-383-5p inhibits the proliferation and migration of lung adenocarcinoma cells by targeting and downregulating SHMT2.
探讨微小RNA-383-5p（miR-383-5p）和丝氨酸羟甲基转移酶2（SHMT2）对肺腺癌细胞增殖和迁移的影响。利用癌症基因组图谱数据库研究肺腺癌组织和正常组织中SHMT2的表达情况。进行免疫组织化学分析以证实肺腺癌组织和邻近正常肺组织中SHMT2的表达。采用生物信息学分析和荧光素酶报告基因检测法分析miR-383-5p与SHMT2表达之间的关系。通过蛋白质免疫印迹法分析SHMT2、波形蛋白、N-钙黏蛋白、E-钙黏蛋白、Bcl-2和细胞周期蛋白D1的蛋白表达水平。采用逆转录定量聚合酶链反应检测SHMT2基因敲低效率、miR-383-5p过表达及抑制效率。使用细胞计数试剂盒-8检测法检测细胞的增殖能力。采用Transwell检测法检测细胞的迁移能力。与对照组患者相比，肺腺癌患者的SHMT2表达显著升高；肺腺癌患者中SHMT2表达越高，预后越差。敲低SHMT2可抑制肺腺癌A549和H1299细胞的增殖、迁移及上皮-间质转化。miR-383-5p可直接靶向并下调A549和H1299细胞中的SHMT2。miRNA-383-5p对这些细胞增殖和迁移的影响与SHMT2不同。外源性过表达SHMT2可逆转miR-383-5p诱导的A549和H1299细胞增殖和迁移抑制。miR-383-5p通过靶向并下调SHMT2抑制肺腺癌细胞的增殖和迁移。
