Involvement of the oncogenic small nucleolar RNA SNORA24 in regulation of p53 stability in colorectal cancer
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. Graphical abstract.
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2022 |
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2022 |
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Zur Gesamtaufnahme - volume:39 |
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Enthalten in: |
Cell biology and toxicology - 39(2022), 4 vom: 10. Sept., Seite 1377-1394 |
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Englisch |
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Beteiligte Personen: |
Shen, Liping [VerfasserIn] |
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Volltext [lizenzpflichtig] |
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© The Author(s), under exclusive licence to Springer Nature B.V. 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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doi: |
10.1007/s10565-022-09765-7 |
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OLC2145004262 |
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520 | |a 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. Graphical abstract | ||
650 | 4 | |a Colorectal cancer (CRC) | |
650 | 4 | |a H/ACA snoRNA | |
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650 | 4 | |a p53 | |
700 | 1 | |a Lin, Chuxian |4 aut | |
700 | 1 | |a Lu, Wenqing |4 aut | |
700 | 1 | |a He, Junyan |4 aut | |
700 | 1 | |a Wang, Qi |4 aut | |
700 | 1 | |a Huang, Yujv |4 aut | |
700 | 1 | |a Zheng, Xiaofei |4 aut | |
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