ISSN : 2146-3123
E-ISSN : 2146-3131

Hsa-miR-217 Inhibits the Proliferation, Migration, and Invasion in Non-small Cell Lung Cancer Cells Via Targeting SIRT1 and P53/KAI1 Signaling
Wenxia Jiang1,2, Likun Hou3, Juan Wei1, Yifeng Du2, Yan Zhao2, Xue Deng4, Xiangdong Lin4
1Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai, China
2Experimental Centre of Medicine and Life Science, Tongji University, Shanghai, China
3Department of Pathology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China
4Tongji University School of Medicine, Shanghai, China
DOI : 10.4274/balkanmedj.galenos.2020.2019.9.91
Pages : 208-214

Abstract

Background: Brain metastasis is a major cause of cancer death in patients with lung cancer. Sirtuin 1 and hsa-miR-217 have been identified to mediate the development of non-small cell lung cancer.
Aims: To investigate the roles of hsa-miR-217, its target sirtuin 1, and the P53/KAI1 axis in the brain metastasis from non-small cell lung cancer.
Study Design: Cell culture study.
Methods: Human pulmonary adenocarcinoma brain metastasis cell line PC-14/B were incubated and treated with constructed lentiviral plasmids expressing miR-217 and/or sirtuin 1. BEAS-2B cell line was used as a control. The targeted regulation of miR-217 to sirtuin 1was examined using a dual-luciferase reporter assay. Cell proliferation, migration, invasion, and related protein expression were detected to examine the effect of the miR-217/sirtuin 1 expression on metastasis.
Results: PC-14/B cells expressed higher sirtuin 1 and lower P53 and KAI1 compared with BEAS-2B control cells (p<0.05). Sirtuin 1 was a direct target of miR-217. MiR-217 expression suppressed PC-14/B cell invasion (p=0.004), migration (p=0.001), and proliferation (p<0.05), whereas sirtuin 1 overexpression reversed all processes. sirtuin 1 expression inhibited P53, KAI1/CD82, matrix metalloproteinase-9, and β-catenin but upregulated E-cadherin protein. MiR-217 overexpression induced reverse changes.
Conclusion: Hsa-miR-217 and its target sirtuin 1 acted as metastasis suppressor and promoter gene in non-small cell lung cancer, respectively. The hsa-miR-217/sirtuin 1/P53/KAI1 metastasis regulatory pathway showed novel and crucial roles in brain metastasis from non-small cell lung cancer. This axis might be a potential target for the treatment of brain metastasis of lung cancer.

Keywords : Brain metastasis, hsa-miRNA-217, lung cancer, PC-14/B cells, sirtuin 1
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