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

Ferro, Iolanda; Gavini, Jacopo; Gallo, Stefano; Bracher, Lisamaria; Landolfo, Marc; Candinas, Daniel; Keogh-Stroka, Deborah M.; Polacek, Norbert (2021). The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome in hepatocellular carcinoma. Autophagy, pp. 1-13. Landes Bioscience 10.1080/15548627.2021.1922983

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Ferro, Iolanda; Gavini, Jacopo; Gallo, Stefano; Bracher, Lisa Maria; Landolfo, Marc Patrick; Candinas, Daniel; Keogh-Stroka, Deborah M. and Polacek, Norbert

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1554-8627

Publisher:

Landes Bioscience

Language:

English

Submitter:

Christina Schüpbach

Date Deposited:

13 Jul 2021 16:28

Last Modified:

14 Jul 2021 16:11

Publisher DOI:

10.1080/15548627.2021.1922983

PubMed ID:

33960270

BORIS DOI:

10.48350/156274

URI:

https://boris.unibe.ch/id/eprint/156274

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