ZNNT1 long noncoding RNA induces autophagy to inhibit tumorigenesis of uveal melanoma by regulating key autophagy gene expression.

Autor:	Li P; Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China.; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, China., He J; Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China.; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, China., Yang Z; Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China.; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, China.; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai, China., Ge S; Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China.; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, China., Zhang H; Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Science and Technology, Tongji University , Shanghai, China., Zhong Q; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, (SJTU-SM) , Shanghai, P.R. China., Fan X; Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China.; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai, China.
Jazyk:	angličtina
Zdroj:	Autophagy [Autophagy] 2020 Jul; Vol. 16 (7), pp. 1186-1199. Date of Electronic Publication: 2019 Sep 03.
DOI:	10.1080/15548627.2019.1659614
Abstrakt:	Long noncoding RNAs (lncRNAs) are proved to be critical regulators in numerous cellular processes. However, the potential involvement of lncRNAs in macroautophagy/autophagy is largely unknown. Autophagy is a highly regulated cellular degradation system, and its dysregulation is involved in many human diseases, including cancers. Here, we show that the lncRNA ZNNT1 is induced by PP242 and MTORC1 selective inhibitor rapamycin in uveal melanoma (UM) cells. Overexpression of ZNNT1 promotes autophagy by upregulating ATG12 expression, whereas knockdown of ZNNT1 attenuates PP242-induced autophagy. Overexpression of ZNNT1 inhibits tumorigenesis and the migration of UM cells, and knockdown of ATG12 can partially rescue the ZNNT1 -induced inhibition of UM tumorigenesis. In summary, our study reveals that ZNNT1 acts as a potential tumor suppressor in UM by inducing autophagy. Abbreviations: ADCD: autophagy dependent cell death; ANXA2R : annexin A2 receptor; ATG12 : autophagy- related 12; ATG5 : autophagy -related 5; ceRNA: competing endogenous RNAs; CQ: chloroquine; iTRAQ: isobaric tags for relative and absolute quantitation; lncRNA: long noncoding RNA; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; MTORC2: MTOR cmplex 2; PP242: Torkinib; RACE: rapid amplification of cDNA ends; SQSTM1 /p62: sequestosome 1; UM: uveal melanoma.
Databáze:	MEDLINE
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