miR-198 targets SHMT1 to inhibit cell proliferation and enhance cell apoptosis in lung adenocarcinoma

• DOI: 10.1007/s13277-015-4369-z
• Publication Date: 2015-11-09T14:46:25Z
• Authors: Shujun Wu; Guojun Zhang; Ping Li; Shanshan Chen; Furui Zhang; Juan Li; Chenyang Jiang; Xiaonan Chen; Yuanyuan Wang; Yuwen Du; Qianqian Sun; Guoqiang Zhao
• Keywords: Adult; Glycine Hydroxymethyltransferase; Male; Lung Neoplasms; Carcinogenesis; Adenocarcinoma of Lung; Apoptosis; Cell Cycle Checkpoints; Adenocarcinoma; Middle Aged; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Lymphatic Metastasis; Humans; Female; Aged; Cell Proliferation

MiR-198 is involved in tumorigenesis, migration, invasion, and metastasis of various malignant cancers. However, the exact expression levels of miR-198 and the molecular mechanism underlying its role in lung adenocarcinoma require further exploration. In this study, quantitative real-time PCR was applied to study miR-198 and serine hydroxymethyltransferase 1 (SHMT1) expression in 47 paired lung adenocarcinoma tissues and adjacent nontumor lung tissues. Clinicopathological characters were analyzed. Pearson's correlation analysis was used to detect the relationship between miR-198 and SHMT1 expression. The function of miR-198 was explored by measuring cell proliferation, cell apoptosis, and the cell-cycle in vitro and in vivo. The target gene of miR-198 was certified using dual luciferase report assay. We found that in lung adenocarcinoma, miR-198 was significantly downregulated and SHMT1 was inversely upregulated. A strong negative correlation was noticed between miR-198 and SHMT1 expression. Further analysis revealed that miR-198 expression was associated with TNM stage and lymph node metastasis. Upregulated miR-198 could inhibit cell proliferation, enhance cell apoptosis, and lead to cell-cycle arrest in lung adenocarcinoma, which showed a more effective alteration than SHMT1 siRNA. Moreover, we identified SHMT1 as a target gene of miR-198. In conclusion, miR-198 suppressed proliferation of lung adenocarcinoma cells both in vitro and in vivo by directly targeting SHMT1. miR-198 may be a potential therapeutic target for lung adenocarcinoma in the near future.