Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2022-09-10 , DOI: 10.1007/s10565-022-09765-7 Liping Shen 1 , Chuxian Lin 1 , Wenqing Lu 1, 2 , Junyan He 3 , Qi Wang 1 , Yujv Huang 1 , Xiaofei Zheng 1 , Zhidong Wang 1
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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
中文翻译：
致癌小核仁 RNA SNORA24 参与结直肠癌 p53 稳定性的调节
结直肠癌（CRC）是世界范围内常见的恶性肿瘤。尽管CRC致癌的分子机制已被广泛研究，但细节仍不清楚。最近有报道称小核仁 RNA (snoRNA) 在致癌作用中具有重要功能，尽管它们在 CRC 发病机制中的作用尚不清楚。在这项研究中，我们发现 H/ACA snoRNA SNORA24 在多种癌症（包括结直肠癌）中表达上调。SNORA24 表达与 CRC 患者队列中的年龄和结肠息肉病史显着相关，高表达与 5 年总生存率下降相关。我们的结果表明，SNORA24 的致癌功能是通过促进 G1/S 期转化、细胞增殖、集落形成和异种移植肿瘤的生长来介导的。此外，SNORA24 敲低诱导大量细胞凋亡。进行 RNA 测序和基因本体 (GO) 富集分析以探索其下游靶点。最后，我们证实 SNORA24 在蛋白酶体降解途径中调节 p53 蛋白的稳定性。我们的研究阐明了 SNORA24 在 CRC 中的致癌作用，并推进了 p53 通路在此过程中作用的当前模型。
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