Knockdown of the snoRNA-Jouvence Blocks the Proliferation and Leads to the Death of Human Primary Glioblastoma Cells

TL;DR

This study shows that reducing the snoRNA-Jouvence in human glioblastoma cells significantly decreases their growth and causes cell death, suggesting a potential new cancer treatment.

Contribution

The study identifies snoRNA-Jouvence as a novel therapeutic target for glioblastoma and AML through its knockdown effects.

Findings

Knockdown of jouvence significantly reduces glioblastoma cell proliferation and induces cell death.

RNA-Seq analysis shows decreased levels of BAALC, a gene linked to oncogenic pathways and cell cycle regulation.

The results suggest potential use of snoRNA-Jouvence knockdown as a new anti-cancer therapy.

Abstract

Background/Objectives: Cancer research aims to understand the cellular and molecular mechanisms involved, in order to identify new therapeutic targets and provide patients with more effective therapies that generate fewer side undesirable and toxic effects. Previous studies have demonstrated the role of small nucleolar RNAs (snoRNAs) in many physiological and pathological cellular processes, including cancers. SnoRNAs are a group of non-coding RNAs involved in different post-transcriptional modifications of ribosomal RNAs. Recently, we identified a new snoRNA (jouvence), first in Drosophila, and thereafter, by homology, in humans. Methods: Here, we characterize the effect of the knockdown of jouvence by a sh-lentivirus on human primary patient-derived glioblastoma cells. Results: The sh-lentivirus anti-jouvence induces a significant decrease in cell proliferation and leads to cell death. EdU staining confirmed this decrease, while TUNEL also showed the presence of apoptotic cells. An RNA-Seq analysis revealed a decrease, in particular, in the level of BAALC, a gene known to potentiate the oncogenic ERK pathway and deregulating p21, leading to cell cycle blockage. Conclusions: Altogether, these results allow the hypothesis that the knockdown of jouvence could potentially be used as a new anti-cancer treatment (sno-Therapy), especially against glioblastoma and also, potentially, against acute myeloid leukemia (AML) due to the BAALC deregulation.

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