SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization
Nkerorema Djodji Damas1, Michela Marcatti1, Christophe Côme1
1Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
Abstract:
We currently have limited knowledge of the involvement of long non-coding RNAs (lncRNAs) in normal cellular processes and pathologies. Here, we identify and characterize SNHG5 as a stable cytoplasmic lncRNA with up-regulated expression in colorectal cancer. Depletion of SNHG5 induces cell cycle arrest and apoptosis in vitro and limits tumour outgrowth in vivo, whereas SNHG5 overexpression counteracts oxaliplatin-induced apoptosis. Using an unbiased approach, we identify 121 transcript sites interacting with SNHG5 in the cytoplasm. Importantly, knockdown of key SNHG5 target transcripts, including SPATS2, induces apoptosis and thus mimics the effect seen following SNHG5 depletion. Mechanistically, we suggest that SNHG5 stabilizes the target transcripts by blocking their degradation by STAU1. Accordingly, depletion of STAU1 rescues the apoptosis induced after SNHG5 knockdown. Hence, we characterize SNHG5 as a lncRNA promoting tumour cell survival in colorectal cancer and delineate a novel mechanism in which a cytoplasmic lncRNA functions through blocking the action of STAU1.
Insights
This study identifies SNHG5, a long non-coding RNA (lncRNA), as crucial for colorectal cancer survival. SNHG5 protects cancer cells by stabilizing target transcripts and inhibiting apoptosis, offering new therapeutic targets.
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Biology
Background:
- Limited understanding of long non-coding RNAs (lncRNAs) in cellular processes and diseases.
- Colorectal cancer (CRC) pathogenesis involves complex molecular mechanisms.
- Identifying novel regulatory molecules in cancer is critical for therapeutic development.
Purpose of the Study:
- To identify and characterize the role of SNHG5, a novel lncRNA, in colorectal cancer.
- To elucidate the molecular mechanism by which SNHG5 influences cancer cell survival and treatment response.
- To explore SNHG5 as a potential therapeutic target in colorectal cancer.
Main Methods:
- Identification and characterization of SNHG5 expression in colorectal cancer.
- In vitro and in vivo functional assays (cell cycle arrest, apoptosis, tumor outgrowth).
- RNA-immunoprecipitation (RIP) and transcriptomic analysis to identify SNHG5 interacting partners.
- Knockdown and overexpression studies of SNHG5, SPATS2, and STAU1.
Main Results:
- SNHG5 is upregulated in colorectal cancer and promotes tumor cell survival.
- SNHG5 depletion induces cell cycle arrest and apoptosis, while its overexpression confers resistance to oxaliplatin.
- SNHG5 stabilizes target transcripts, including SPATS2, by inhibiting STAU1-mediated degradation, thereby promoting cancer cell survival.
Conclusions:
- SNHG5 is a cytoplasmic lncRNA that enhances colorectal cancer cell survival.
- SNHG5 functions by stabilizing target transcripts through the inhibition of STAU1.
- SNHG5 represents a potential therapeutic target for colorectal cancer treatment.
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