Shen Liping, Lin Chuxian, Lu Wenqing, He Junyan, Wang Qi, Huang Yujv, Zheng Xiaofei, Wang Zhidong
Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
College of Life Sciences, Hebei University, Baoding, Hebei, 071002, China.
Cell Biol Toxicol. 2023 Aug;39(4):1377-1394. doi: 10.1007/s10565-022-09765-7. Epub 2022 Sep 10.
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.
结直肠癌（CRC）是全球常见的恶性肿瘤。尽管对CRC致癌作用的分子机制已进行了广泛研究，但细节仍不清楚。小核仁RNA（snoRNAs）最近被报道在致癌过程中具有重要功能，尽管它们在CRC发病机制中的作用大多未知。在本研究中，我们发现H/ACA snoRNA SNORA24在包括CRC在内的多种癌症中上调。在CRC患者队列中，SNORA24表达与年龄和结肠息肉病史显著相关，高表达与5年总生存率降低相关。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生长来介导的。此外，SNORA24敲低诱导大量细胞凋亡。进行了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途径在此过程中作用的当前模型。
