The knockdown of the snoRNA-jouvence blocks the cell proliferation and leads to cell death of human primary cancerous glioblastoma cells

Abstract

ABSTRACTCancer research aims to identify new therapeutic targets and provide patients with more effective therapies that generate fewer deleterious side 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 have identified a new snoRNA, namedjouvence(snoRNA-jou) in humans. Here, we characterize the effect of the knockdown of the snoRNA-jouvence by sh-lentivirus on human primary glioblastoma cells. The sh-lentivirus induces a significant decrease of cell proliferation, proportional to the amount of lentivirus used. For example, with a MOI-20, a decrease of more than 50% is observed after only 72 hours, and even up to 80% after 10 days. Moreover, a EdU proliferative test confirms this decrease in cell proliferation, while a TUNEL test reveals the presence of apoptotic cells. A RNA-Seq analysis, validated by RT-qPCR, reveals that the snoRNA-jou knockdown induces a significant deregulation of several key genes involved in the cell cycle regulation, such as cyclins B1, A2 and p21, indicating a cell cycle blockage. Altogether, these results allow hypothesising that the knockdown of the snoRNA-jouvence could potentially be use as a new anti-cancer treatment (sno-Therapy).