Downregulation of NUDT21 contributes to cervical cancer progression through alternative polyadenylation
Downregulation of NUDT21 contributes to cervical cancer progression through alternative polyadenylation
复制标题
NUDT21 下调通过替代多聚腺苷酸化促进宫颈癌进展
DOI：
10.1038/s41388-021-01693-w
复制
发表时间：
2021-02-22
期刊：
影响因子：
8
通讯作者：
Hou, Teng
中科院分区：
文献类型：
--
作者：
Xing, Yifei;Chen, Liang;Hou, Teng
Nudix水解酶21 （NUDT21）是一种选择性多聚腺苷化（APA）调节蛋白，具有肿瘤抑制作用。然而，其在宫颈癌（CxCa）中的作用尚不清楚。在本研究中，我们发现CxCa组织和细胞中NUDT21表达降低，并且NUDT21水平与CxCa患者的临床预后高度相关。敲低NUDT21可促进体外CxCa细胞的增殖、迁移和侵袭，促进体内肿瘤发生和肺转移。过表达NUDT21会产生相反的效果。此外，我们进行了多聚腺苷化位点测序（PAS-Seq），并在NUDT21过表达时鉴定出457个具有延长的3 ‘非翻译区（3 ’ utr）的转录本。特别是，NUDT21调节了几个参与脂肪酸代谢的基因的表达，以及CxCa发育中的Wnt和NF-κB信号通路。综上所述，我们的研究表明，NUDT21的APA调控作用是CxCa抑制的重要机制。
Nudix Hydrolase 21 (NUDT21), an alternative polyadenylation (APA)-regulatory protein, exhibits tumor-suppressive effects. However, its role in cervical cancer (CxCa) remains unknown. In the present study, we found that NUDT21 expression was reduced in CxCa tissues and cells, and NUDT21 levels were highly associated with the clinical prognosis of patients with CxCa. Knockdown of NUDT21 promoted CxCa cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and lung metastasis in vivo. Overexpression of NUDT21 produces the opposite effects. Moreover, we performed polyadenylation site sequencing (PAS-Seq) and identified 457 transcripts with lengthened 3′ untranslated regions (3′ UTRs) upon NUDT21 overexpression. In particular, NUDT21 modulated the expression of several genes involved in fatty acid metabolism and the Wnt and NF-κB signaling pathways in CxCa development. Taken together, our study demonstrated that the APA regulatory effect of NUDT21 is an important mechanism for CxCa suppression.