MEX3A is upregulated in esophageal squamous cell carcinoma (ESCC) and promotes development and progression of ESCC through targeting CDK6.
MEX3A is upregulated in esophageal squamous cell carcinoma (ESCC) and promotes development and progression of ESCC through targeting CDK6.
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DOI：
10.18632/aging.103196
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发表时间：
2020-11-14
期刊：
影响因子：
--
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Wei L;Wang B;Hu L;Xu Y;Li Z;Shen Y;Huang H
食管鳞状细胞癌(ESCC)是世界范围内最常见的恶性肿瘤之一，严重威胁人类健康。MEX3A在食管鳞癌中的作用尚不清楚。在本研究中，我们发现MEX3A在食管鳞癌组织中表达上调，并与肿瘤分期越高、淋巴转移风险越高、预后越差呈正相关。MEX3A表达下调可抑制细胞增殖、集落形成、迁移，促进细胞凋亡，而MEX3A过表达则相反。体内实验也证实了MEX3A基因敲除对ESCC的抑制作用。此外，我们发现CDK6是MEX3A的潜在靶点，MEX3A在ESCC中也表达上调。进一步研究表明，CDK6基因敲除在食管癌的发生发展中与MEX3A表现出相似的作用。更重要的是，CDK6基因敲除可以减轻MEX3A过表达对ESCC的促进作用。综上所述，通过靶向CDK6，MEX3A被认为是ESCC发生发展过程中的肿瘤促进剂，可作为ESCC治疗的一个新的预后指标和治疗靶点。
Esophageal squamous cell carcinoma (ESCC) is one of the most commonly diagnosed malignant tumors worldwide and identified as a serious threat to human health. The role of MEX3A in ESCC remains unclear. In this study, we found that MEX3A was upregulated in tumor tissues of ESCC and positively associated with more advanced tumor stage, higher risk of lymphatic metastasis and poor prognosis. The downregulation of MEX3A in ESCC cell lines could induce inhibition of cell proliferation, colony formation, cell migration, and the promotion of cell apoptosis, while MEX3A overexpression exhibited opposite effects. In vivo experiments also verified the inhibition of ESCC induced by MEX3A knockdown. Moreover, we identified CDK6 as a potential target of MEX3A, which was also upregulated in ESCC. Further studies demonstrated that knockdown of CDK6 showed similar effects on the development of ESCC with MEX3A. More importantly, it was illustrated that CDK6 knockdown could alleviate the promotion effects of MEX3A overexpression on ESCC. In conclusion, MEX3A was identified as a tumor promotor in the development and progression of ESCC by targeting CDK6, which may be considered as a novel prognostic indicator and therapeutic target in treatment of ESCC.
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影响因子：
37.3
作者：
Kashyap MK;Abdel-Rahman O
通讯作者：
Abdel-Rahman O
影响因子：
5.6
作者：
Miyamoto Y;Suyama K;Baba H
通讯作者：
Baba H
影响因子：
2.6
作者：
Baba, Yoshifumi;Baba, Hideo;Aiba, Keisuke
通讯作者：
Aiba, Keisuke
影响因子：
1.3
作者：
Krepischi ACV;Maschietto M;Ferreira EN;Silva AG;Costa SS;da Cunha IW;Barros BDF;Grundy PE;Rosenberg C;Carraro DM
通讯作者：
Carraro DM
影响因子：
51.1
作者：
Dutton, Susan J.;Ferry, David R.;Petty, Russell D.
通讯作者：
Petty, Russell D.