The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome in hepatocellular carcinoma

作     者：Ferro, Iolanda Gavini, Jacopo Gallo, Stefano Bracher, Lisamaria Landolfo, Marc Candinas, Daniel Stroka, Deborah M. Polacek, Norbert 

作者机构：Univ Bern Dept Chem Biochem & Pharmaceut Sci Freiestr 3 CH-3012 Bern Switzerland Bern Univ Hosp Inselspital Dept BioMed Res Dept Visceral Surg & Med Bern Switzerland Univ Bern Bern Switzerland Univ Bern Grad Sch Cellular & Biomed Sci Bern Switzerland 

出 版 物：《AUTOPHAGY》 (自体吞噬)

年 卷 期：2022年第18卷第1期

页      面：191-203页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：NCCR "RNA & Disease" - Swiss National Science Foundation Ruth and Arthur Scherbarth Foundation Aclon Foundation 

主　　题：Chemoresistance lysosome non-coding RNA tumorigenesis vault RNA vtRNA1-1 

摘      要：The small non-coding VTRNA1-1 (vault RNA 1-1) is known to confer resistance to apoptosis in several malignant cell lines and to also modulate the macroautophagic/autophagic flux in hepatocytes, thus highlighting its pro-survival role. Here we describe a new function of VTRNA1-1 in regulating in vitro and in vivo tumor cell proliferation, tumorigenesis and chemoresistance. Knockout (KO) of VTRNA1-1 in human hepatocellular carcinoma cells reduced nuclear localization of TFEB (transcription factor EB), leading to a downregulation of the coordinated lysosomal expression and regulation (CLEAR) network genes and lysosomal compartment dysfunction. We demonstrate further that impaired lysosome function due to loss of VTRNA1-1 potentiates the anticancer effect of conventional chemotherapeutic drugs. Finally, loss of VTRNA1-1 reduced drug lysosomotropism allowing higher intracellular compound availability and thereby significantly reducing tumor cell proliferation in vitro and in vivo. These findings reveal a so far unknown role of VTRNA1-1 in the intracellular catabolic compartment and describe its contribution to lysosome-mediated chemotherapy resistance.