SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization

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.

lncRNA SNHG5 is associated with poor prognosis of bladder cancer and promotes bladder cancer cell proliferation through targeting p27

“…Zhao et al demonstrated that overexpressed SNHG5 significantly represses the progression of gastric cancer (17,26). While, Damas et al uncovered that high level of SNHG5 obviously promotes cell survival in colorectal cancer (16). Consistently, our study also presented tumor-promoting function of SNHG5.…”

“…Cui et al uncovered that upregulated lncRNA SNHG1 contributed to progression of non-small cell lung cancer through inhibition of miR-101-3p and activation of Wnt/β-catenin signaling pathway (25). SNHG5 is anomalously expressed in human gastric cancer and colorectal cancer (16,17). However, its biological function in BC has not been investigated.…”

“…These results suggested that SNHG5 expression might be associated with the level of malignancy of BC, and might be involved in the tumorigenesis and progression of BC. It has been demonstrated that the effect of SNHG5 is related with its biological function on cell proliferation (16,17). Therefore, we explored the biological function of SNHG5 in BC cells.…”

“…Small nucleolar RNA host gene 5 (SNHG5), a SnoRNA-U50-associated lncRNA, has been demonstrated downregulated in bladder cancer (BC) and colorectal carcinoma (CRC) (16,17). However, its biological function in BC has not been investigated.…”

Non-coding RNA: It’s Not Junk

“…[11] Adding to this, Gao et al have revealed that CRNDE functions like a miRNA sponge, downregulating miR-136 , conferring resistance to the chemotherapeutic agent oxaliplatin. [12].…”