MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS.
MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS.
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MEX3A通过调节TIMELESS中的内含子保留促进卵巢癌的恶性进展
DOI：
10.1038/s41419-022-05000-7
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发表时间：
2022-06-17
影响因子：
9
通讯作者：
Li, Yingwei
中科院分区：
文献类型：
--
作者：
Li, Fangfang;Zhao, Chen;Diao, Yuchao;Wang, Zixiang;Peng, Jiali;Yang, Ning;Qiu, Chunping;Kong, Beihua;Li, Yingwei
最新的研究表明，RNA结合蛋白（RBP）可能成为癌症治疗的新的潜在靶点。我们利用生物信息学分析筛选和鉴定了卵巢癌中的关键RBP，从中发现Mex-3 RNA结合家族成员A（MEX 3A）与卵巢癌的临床预后密切相关。然而，人们对其在卵巢癌中的生物学作用知之甚少。在这种情况下，我们观察到MEX 3A在新鲜冷冻的卵巢癌组织中高度过表达。MEX 3A基因敲低抑制卵巢癌细胞的生长和侵袭，而MEX 3A基因过表达促进卵巢癌细胞的增殖和侵袭。从机制上讲，TIMELESS是MEX 3A的关键下游靶基因，如通过基于RNA-seq的选择性剪接事件分析所证明的。MEX 3A敲低导致TIMELESS mRNA的内含子23保留，并且由于无义介导的RNA衰变（NMD）的刺激而减少TIMELESS mRNA。此外，我们发现TIMELESS过表达与MEX 3A敲低部分恢复卵巢癌细胞的增殖能力。本论文的结果表明，MEX 3A/TIMELESS信号通路是卵巢癌的关键调节因子，MEX 3A是卵巢癌患者的一个新的可能的治疗靶点。
The latest research shows that RNA-binding proteins (RBPs) could serve as novel potential targets for cancer therapy. We used bioinformatics analysis to screen and identify the key RBPs in ovarian cancer, from which we found that Mex-3 RNA Binding Family Member A (MEX3A) was intimately associated with the clinical prognosis of ovarian cancer. Nevertheless, little is known about its biological roles in ovarian cancer. In this case, we observed that MEX3A was highly overexpressed in fresh-frozen ovarian cancer tissues. MEX3A knockdown suppressed the development and invasion of ovarian cancer cells, while MEX3A overexpression promoted the proliferation and invasion of ovarian cancer cells. Mechanistically, TIMELESS was the critical downstream target gene of MEX3A, as demonstrated through alternative splicing event analysis based on RNA-seq. MEX3A knockdown resulted in retention of intron twenty-three of TIMELESS mRNA and decreased TIMELESS mRNA owing to stimulation of nonsense-mediated RNA decay (NMD). Additionally, we found that TIMELESS overexpression with MEX3A knockdown partially restored the proliferation ability of ovarian cancer cells. The results of this paper demonstrated that the MEX3A/TIMELESS signaling pathway was a key regulator of ovarian cancer, and MEX3A was a novel possible treatment target for ovarian cancer patients.
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影响因子：
9
作者：
Wang S;Wang Z;Li J;Qin J;Song J;Li Y;Zhao L;Zhang X;Guo H;Shao C;Kong B;Liu Z
通讯作者：
Liu Z
影响因子：
51.1
作者：
Arnold, Melina;Rutherford, Mark J.;Bray, Freddie
通讯作者：
Bray, Freddie
DOI：
10.18632/aging.103196
发表时间：
2020-11-14
期刊：
Aging
影响因子：
--
作者：
Wei L;Wang B;Hu L;Xu Y;Li Z;Shen Y;Huang H
通讯作者：
Huang H
DOI：
10.4161/cc.21989
发表时间：
2012-11-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Leman AR;Noguchi E
通讯作者：
Noguchi E
通过小 RNA 干扰敲低 hMex-3A 可抑制人胃癌细胞的细胞增殖和迁移。
影响因子：
3.4
作者：
Jiang, Hong;Zhang, Xuemei;Yang, Changqing
通讯作者：
Yang, Changqing