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Tumour Biol. 2016 Apr;37(4):5193-202. doi: 10.1007/s13277-015-4369-z. Epub 2015 Nov 9.

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

Author information

1
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People' s Republic of China.
2
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People' s Republic of China. gjzhangzzu@126.com.
3
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People' s Republic of China.
4
School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, People' s Republic of China.
5
School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, People' s Republic of China. zhaogq@zzu.edu.cn.

Abstract

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.

KEYWORDS:

Apoptosis; Lung adenocarcinoma; MiR-198; Proliferation; Serine hydroxymethyltransferase 1

PMID:
26553359
DOI:
10.1007/s13277-015-4369-z
[Indexed for MEDLINE]

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