SNORD88C guided 2′-O-methylation of 28S rRNA regulates SCD1 translation to inhibit autophagy and promote growth and metastasis in non-small cell lung cancer
SNORD88C guided 2′-O-methylation of 28S rRNA regulates SCD1 translation to inhibit autophagy and promote growth and metastasis in non-small cell lung cancer
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DOI：
10.1038/s41418-022-01087-9
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发表时间：
2022-11-14
影响因子：
12.4
通讯作者：
Song, Xianrang
中科院分区：
文献类型：
--
作者：
Wang, Kangyu;Wang, Shiwen;Song, Xianrang
小核仁RNA（snoRNA）已被证明在癌症发展中起关键的调节作用。通过数据库和snoRNA测序，筛选到位于染色体19q.33上C19 orf 48内含子区的97个核苷酸的SNORD 88 C。我们首先验证了该snoRNA在组织和血浆中表达上调，并作为非侵入性诊断生物标志物;然后证实了SNORD 88 C在体外和体内促进NSCLC的增殖和转移。SNORD 88 C通过促进28 S rRNA上C3680位点的2 '-O-甲基化修饰，进而增强下游SCD 1的翻译，SCD 1是合成MUFA的中心脂肪生成酶，可通过调节脂质过氧化和mTOR抑制自噬，为研究SNORD 88 C在NSCLC中的调控提供了新的视角。
Small nucleolar RNAs (snoRNAs) have been shown to play critical regulatory roles in cancer development. SNORD88C, which located at the intronic region of C19orf48 in chromosome 19q.33 with a 97-nt length was screened through database and snoRNA-sequencing. We firstly verified this snoRNA was up-regulated in tissue and plasma and served as a non-invasive diagnostic biomarker; then confirmed that SNORD88C promoted proliferation and metastasis of NSCLC in vitro and in vivo. Mechanistically, SNORD88C promoted 2 '-O-methylation modification at the C3680 site on 28S rRNA and in turn enhanced downstream SCD1 translation, a central lipogenic enzyme for the synthesis of MUFA that can inhibit autophagy by regulating lipid peroxidation and mTOR, providing the novel insight into the regulation of SNORD88C in NSCLC.