Gang Li et al., at Department of Neurosurgery, Qilu Hospital, Shandong University, China, presented a comprehensive study on the role of regulator of G-protein signaling 16 (RGS16) in the progression of glioma, a highly aggressive central nervous system tumor. Glioma accounts for over 70% of all brain tumors and has a particularly lethal form, glioblastoma (GB), with an average survival time of 12–15 months. Despite advancements in diagnostic and therapeutic strategies, glioma remains challenging to treat, highlighting the urgency for novel treatment approaches.
RGS proteins, including RGS16, are known to negatively regulate G-protein signaling pathways, which are implicated in various cancer-related processes such as cell migration, invasion, proliferation, chemoresistance, and metastasis. However, the specific role of RGS16 in glioma has not been fully explored. MicroRNAs (miRNAs), small noncoding RNAs, are significant posttranscriptional regulators of gene expression and can act as tumor suppressors, including let-7c-5p, which is hypothesized to regulate RGS16.
This research investigates the impact of RGS16 on glioma cells and its regulation by let-7c-5p. The study employs a range of methods, from bioinformatics analysis to in vitro and in vivo experiments, to assess the role of RGS16. The Cox proportional hazards model is utilized to identify genes associated with survival, and tissue samples and cell lines are analyzed to study the expression patterns of RGS16 in glioma tissues.
The findings indicate that RGS16 is upregulated in glioma tissues and is associated with unfavorable patient outcomes. The knockdown of RGS16 in glioma cells inhibits cell proliferation, migration, and invasion both in vitro and in vivo. The study also reveals that RGS16 activates the PI3K-AKT pathway, a critical signaling mechanism in cancer progression, suggesting that RGS16 may promote glioma progression by this route.
Furthermore, the research identifies let-7c-5p as a regulator of RGS16. The overexpression of let-7c-5p is shown to inhibit glioma cell proliferation, migration, and invasion, while its knockdown has the opposite effect. The study confirms the targeting relationship between let-7c-5p and RGS16 through a luciferase reporter assay and an AGO2 RNA immunoprecipitation assay.
In conclusion, the study suggests that RGS16, regulated by let-7c-5p, is an oncogenic molecule in glioma and may serve as a potential therapeutic target. The findings contribute to a better understanding of the molecular mechanisms underlying glioma progression and identify a novel target for glioma treatment. However, the study acknowledges limitations, such as the need for further investigation into the precise molecular mechanisms of the interaction between RGS16 and let-7c-5p.
DOI: 10.1007/s11684-022-0929-y