Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells

Bracher, Lisamaria; Ferro, Iolanda; Pulido-Quetglas, Carlos; Ruepp, Marc‐David; Johnson, Rory; Polacek, Norbert

doi:10.3390/biom10040614

Cited by 31 publications

(61 citation statements)

References 55 publications

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“…Accumulating evidence revealing a key role of the small non-coding vtRNA1-1 in conferring cellular resistance against cell death via chemoresistance 7,12 and viral defence and apoptosis 4,8,13,48 , lead us to further investigate the involvement of vtRNA1-1 in tumorigenesis and cancer progression. In agreement with its previously described function, we observed a modulation of vtRNA1-1 expression in response to apoptosis induced by physical and mechanical stress in primary human hepatocytes and liver-derived clinical biopsies (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, in Hela cells, where vtRNA1-1 was shown to confer apoptosis resistance ( Fig. 2b and 8,13 , neither changes in lysosomal pH nor in its proteolytic activity were apparent when vtRNA1-1 was depleted ( Fig. S3a, b).…”

Section: Vtrna1-1 Loss Increases Autophagic Flux Progression and Enhamentioning

confidence: 97%

“…The anti-apoptotic effect of vtRNA1-1 has been the subject of intensive studies in our laboratory 8,13 and lead us to hypothesize about its involvement in tumorigenesis and cancer progression. To test the influence of vtRNA1-1 expression on tumor cell proliferation and colony formation in vitro, we used the human hepatocellular carcinoma cell lines HuH-7 (wt), HuH-7 vtRNA1-1 KO and HuH-7 vtRNA1-1 complementation cells, in which vtRNA1-1 was ectopically expressed by lentiviral transduction of KO cells ( Fig.…”

Section: Vtrna1-1 Plays a Crucial Role In Tumor Cell Proliferation Anmentioning

confidence: 99%

“…Since vtRNA1-1 levels have been reported previously to affect apoptosis 8,13 and autophagy 9 , we next asked the question how and if these cellular processes are linked via vtRNA1-1 expression in hepatocytes. HuH-7 sensitivity towards apoptosis was not affected by vtRNA1-1 depletion, since upon staurosporine treatment, a broad-spectrum protein kinase inhibitor inducing apoptosis, the IC 50 values were similar for both wt and vtRNA1-1 KO cell lines ( Fig.…”

Section: Vtrna1-1 Loss Increases Autophagic Flux Progression and Enhamentioning

confidence: 99%

“…Many of these findings are compatible with the hypothesis that altered vtRNA expression is associated with tumorigenesis. Recently, we demonstrated that the vtRNA1-1 paralog protects various human cancer cell lines from undergoing apoptosis in a vault particle-independent manner 8,13 . Yet, the exact function and mechanism of action of vault RNAs remains undeciphered in molecular terms.…”

Section: Introductionmentioning

confidence: 99%

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The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome

Ferro

Gavini

Bracher

et al. 2020

Preprint

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The small non-coding vault RNA (vtRNA) 1-1 has been shown to confer apoptosis resistance in several malignant cell lines and also to modulate the 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. By activating extracellular signal-regulated kinases (ERK 1/2), vtRNA1-1 knock-out (KO) inhibits transcription factor EB (TFEB), leading to a downregulation of the coordinated lysosomal expression and regulation (CLEAR) network genes and lysosomal compartment dysfunction. Pro-tumorigenic pathways dysregulation and decreased lysosome functionality potentiate the anticancer effect of conventional targeted cancer drugs in the absence of vtRNA1-1. Finally, vtRNA1-1 KO-reduced lysosomotropism, together with a higher intracellular compound availability, significantly reduced tumor cell proliferation in vitro and in vivo. These findings reveal the role of vtRNA1-1 in ensuring intracellular catabolic compartment stability and functionality, suggesting its importance in lysosome-mediated chemotherapy resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Vtrna1-1 Loss Increases Autophagic Flux Progression and Enhamentioning

confidence: 97%

Section: Vtrna1-1 Plays a Crucial Role In Tumor Cell Proliferation Anmentioning

confidence: 99%

Section: Vtrna1-1 Loss Increases Autophagic Flux Progression and Enhamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome

Ferro

Gavini

Bracher

et al. 2020

Preprint

Self Cite

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The Pol III transcriptome: Basic features, recurrent patterns, and emerging roles in cancer

Zhou

Bortle

2023

WIREs RNA

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The RNA polymerase III (Pol III) transcriptome is universally comprised of short, highly structured noncoding RNA (ncRNA). Through RNA–protein interactions, the Pol III transcriptome actuates functional activities ranging from nuclear gene regulation (7SK), splicing (U6, U6atac), and RNA maturation and stability (RMRP, RPPH1, Y RNA), to cytoplasmic protein targeting (7SL) and translation (tRNA, 5S rRNA). In higher eukaryotes, the Pol III transcriptome has expanded to include additional, recently evolved ncRNA species that effectively broaden the footprint of Pol III transcription to additional cellular activities. Newly evolved ncRNAs function as riboregulators of autophagy (vault), immune signaling cascades (nc886), and translation (Alu, BC200, snaR). Notably, upregulation of Pol III transcription is frequently observed in cancer, and multiple ncRNA species are linked to both cancer progression and poor survival outcomes among cancer patients. In this review, we outline the basic features and functions of the Pol III transcriptome, and the evidence for dysregulation and dysfunction for each ncRNA in cancer. When taken together, recurrent patterns emerge, ranging from shared functional motifs that include molecular scaffolding and protein sequestration, overlapping protein interactions, and immunostimulatory activities, to the biogenesis of analogous small RNA fragments and noncanonical miRNAs, augmenting the function of the Pol III transcriptome and further broadening its role in cancer.This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Processing of Small RNAs RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications

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Vault RNAs: hidden gems in RNA and protein regulation

Hahne

Lampis

Valeri

2020

Cell. Mol. Life Sci.

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Non-coding RNAs are important regulators of differentiation during embryogenesis as well as key players in the fine-tuning of transcription and furthermore, they control the post-transcriptional regulation of mRNAs under physiological conditions. Deregulated expression of non-coding RNAs is often identified as one major contribution in a number of pathological conditions. Non-coding RNAs are a heterogenous group of RNAs and they represent the majority of nuclear transcripts in eukaryotes. An evolutionary highly conserved sub-group of non-coding RNAs is represented by vault RNAs, named since firstly discovered as component of the largest known ribonucleoprotein complexes called “vault”. Although they have been initially described 30 years ago, vault RNAs are largely unknown and their molecular role is still under investigation. In this review we will summarize the known functions of vault RNAs and their involvement in cellular mechanisms.

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Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells

Cited by 31 publications

References 55 publications

The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome

The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome

The Pol III transcriptome: Basic features, recurrent patterns, and emerging roles in cancer

Vault RNAs: hidden gems in RNA and protein regulation

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