LINC00857 Interacting with YBX1 to Regulate Apoptosis and Autophagy via MET and Phosphor-AMPKa Signaling

Su，Wenmei1; Wang，Lihui2; Zhao，Huijie3; Hu，Shengmin3; Zhou，Yi3; Guo，Chunfang4; Wu，Bin1; Li，Lixia1; Yang，Zhixiong1; Beer，David G.4; Chen，Guoan3

2020-12-04

10.1016/j.omtn.2020.10.025

Molecular Therapy-Nucleic Acids   影响因子和分区

2162-2531

2162-2531

Long noncoding RNA (lncRNA) LINC00857 has been reported to be upregulated in lung cancer and related to poor patient survival. It can regulate cell proliferation and tumor growth in lung cancer as well as several other cancers. However, the underlying molecular mechanisms that are regulated by LINC00857 are unclear. In this study, we found that LINC00857 silencing can impair cell proliferation in 14 different genomic alterations of lung cancer cell lines. These alterations are EGFR, KRAS, TP53, MET, and LKB1 mutations. The cell apoptosis and autophagy were induced upon LINC00857 silencing in lung cancer cells. Mechanistically, LINC00857 can bind to the Y-box binding protein 1 (YBX1) protein, prevent it from proteasomal degradation, and increase its nuclear translocation. LINC00857 regulated MET expression via YBX1 at a transcriptional level. Induced cell autophagy by LINC00857 knockdown was mainly through increased phosphor-AMP-activated protein kinase (p-AMPK)a. Collectively, LINC00857-YBX1-MET/p-AMPKa signaling is critical to regulate cell proliferation, apoptosis, and autophagy, which may provide a potential clinically therapeutic target in lung cancer.

apoptosis autophagy LINC00857 lung cancer YBX1

SCI

英语

通讯

National Natural Science Foundation of China (NSFC), China[32070625,82073388,81803564,81871883] ; Affiliated Hospital of Guangdong Medical University Doctoral Foundation[2018052638] ; China Postdoctoral Science Foundation, China[2018M633619XB]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:000596789800005

CELL PRESS

2-s2.0-85096618621

Scopus

1.Department of Pulmonary Oncology,Affiliated Hospital of Guangdong Medical University,Zhanjiang,China
2.Key Laboratory of Longevity and Aging-Related Diseases of Chinese Ministry of Education,Center for Translational Medicine & School of Preclinical Medicine,Guangxi Medical University,Nanning,China
3.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
4.Department of Surgery,University of Michigan,Ann Arbor,United States

Su，Wenmei,Wang，Lihui,Zhao，Huijie,et al. LINC00857 Interacting with YBX1 to Regulate Apoptosis and Autophagy via MET and Phosphor-AMPKa Signaling[J]. Molecular Therapy-Nucleic Acids,2020,22:1164-1175.

Su，Wenmei.,Wang，Lihui.,Zhao，Huijie.,Hu，Shengmin.,Zhou，Yi.,...&Chen，Guoan.(2020).LINC00857 Interacting with YBX1 to Regulate Apoptosis and Autophagy via MET and Phosphor-AMPKa Signaling.Molecular Therapy-Nucleic Acids,22,1164-1175.

Su，Wenmei,et al."LINC00857 Interacting with YBX1 to Regulate Apoptosis and Autophagy via MET and Phosphor-AMPKa Signaling".Molecular Therapy-Nucleic Acids 22(2020):1164-1175.