Abstract
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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All data is available in the main text and supplementary materials. All models, nucleotide sequences, vectors, or plasmids used in the study are available from the corresponding author upon reasonable request.
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Acknowledgements
We thank Dr. QT Zhang (Liaoning Cancer Hospital) for kindly providing clinical samples.
Funding
This work was supported by grant from the National Natural Science Foundation of China [32071240 to Zhidong Wang] and China Postdoctoral Science Foundation (2020M673684 to Liping Shen).
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Study concept and design (Zhidong Wang, Xiaofei Zheng); experimental operation (Liping Shen, Chuxian Lin, Wenqing Lu, Yujv Huang); analysis of data (Liping Shen, Junyan He, Qi Wang); drafting of the manuscript (Liping Shen, Zhidong Wang).
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Written informed consent was obtained from participants. Clinical samples used in this study have been reviewed and approved by the Ethics Committee on Human Investigation of the Liaoning Cancer Hospital (20190970). Animal experiments were approved by the Ethics Committee of AMMS (IACUC-DWZX-2020–549, Beijing, China).
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Shen, L., Lin, C., Lu, W. et al. Involvement of the oncogenic small nucleolar RNA SNORA24 in regulation of p53 stability in colorectal cancer. Cell Biol Toxicol 39, 1377–1394 (2023). https://doi.org/10.1007/s10565-022-09765-7
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DOI: https://doi.org/10.1007/s10565-022-09765-7