Involvement of the oncogenic small nucleolar RNA SNORA24 in regulation of p53 stability in colorectal cancer

癌变 癌症研究 生物 结直肠癌 癌症 小核仁RNA 基因敲除 下调和上调 长非编码RNA 微卫星不稳定性 核糖核酸 基因 遗传学 微卫星 等位基因
作者
Liping Shen,Chuxian Lin,Wenqing Lü,Junyan He,Qi Wang,Yujv Huang,Xiaofei Zheng,Zhidong Wang
出处
期刊:Cell Biology and Toxicology [Springer Science+Business Media]
卷期号:39 (4): 1377-1394 被引量:5
标识
DOI:10.1007/s10565-022-09765-7
摘要

Colorectal cancer (CRC) is a common malignant cancer worldwide. Although the molecular mechanism of CRC carcinogenesis has been studied extensively, the details remain unclear. Small nucleolar RNAs (snoRNAs) have recently been reported to have essential functions in carcinogenesis, although their roles in CRC pathogenesis are largely unknown. In this study, we found that the H/ACA snoRNA SNORA24 was upregulated in various cancers, including CRC. SNORA24 expression was significantly associated with age and history of colon polyps in CRC patient cohorts, with high expression associated with a decreased 5-year overall survival. Our results indicated that the oncogenic function of SNORA24 is mediated by promoting G1/S phase transformation, cell proliferation, colony formation, and growth of xenograft tumors. Furthermore, SNORA24 knockdown induced massive apoptosis. RNA-sequencing and gene ontology (GO) enrichment analyses were performed to explore its downstream targets. Finally, we confirmed that SNORA24 regulates p53 protein stability in a proteasomal degradation pathway. Our study clarifies the oncogenic role of SNORA24 in CRC and advance the current model of the role of the p53 pathway in this process.
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