UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis
UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis
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UPF1 通过 eIF2α-ATF4 轴增加氨基酸水平并促进肺腺癌细胞增殖
DOI：
10.1631/jzus.b2200144
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发表时间：
2022-10
影响因子：
5.1
通讯作者：
Chundong Gu
中科院分区：
文献类型：
--
作者：
Lei Fang;Huan Qi;Peng Wang;Shiqing Wang;Tianjiao Li;Tian Xia;Hailong Piao;Chundong Gu
上移码1 （UPF1）作为无义介导的信使RNA （mRNA）衰变（NMD）中最关键的因子，在许多癌症中调节肿瘤相关的分子通路。然而，UPF1在肺腺癌（LUAD）氨基酸代谢中的作用在很大程度上仍然未知。在本研究中，我们通过生物信息学和代谢组学的结合，发现UPF1与LUAD中部分氨基酸代谢途径显著相关。我们进一步证实，UPF1敲低抑制了激活转录因子4 （ATF4）和真核翻译起始因子2α (eIF2α)的Ser51磷酸化，这是氨基酸代谢重编程的核心蛋白。此外，UPF1通过增加LUAD细胞的氨基酸水平来促进细胞增殖，这依赖于ATF4的功能。临床上，UPF1 mRNA在LUAD组织中表达异常，UPF1和ATF4的高表达与LUAD患者总生存期（OS）较差显著相关。我们的研究结果表明，UPF1是肿瘤相关氨基酸代谢的潜在调节剂，可能是LUAD的治疗靶点。
Up-frameshift 1 (UPF1), as the most critical factor in nonsense-mediated messenger RNA (mRNA) decay (NMD), regulates tumor-associated molecular pathways in many cancers. However, the role of UPF1 in lung adenocarcinoma (LUAD) amino acid metabolism remains largely unknown. In this study, we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics. We further confirmed that UPF1 knockdown inhibited activating transcription factor 4 (ATF4) and Ser51 phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), the core proteins in amino acid metabolism reprogramming. In addition, UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells, which depends on the function of ATF4. Clinically, UPF1 mRNA expression is abnormal in LUAD tissues, and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival (OS) in LUAD patients. Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.
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影响因子：
29
作者：
Lee JV;Carrer A;Shah S;Snyder NW;Wei S;Venneti S;Worth AJ;Yuan ZF;Lim HW;Liu S;Jackson E;Aiello NM;Haas NB;Rebbeck TR;Judkins A;Won KJ;Chodosh LA;Garcia BA;Stanger BZ;Feldman MD;Blair IA;Wellen KE
通讯作者：
Wellen KE
影响因子：
8.8
作者：
Newman AC;Maddocks ODK
通讯作者：
Maddocks ODK
NEDD8 结合酶 E2 UBE2F 通过保护肺癌细胞免于凋亡而赋予辐射抗性
DOI：
10.1631/jzus.b2100170
发表时间：
2021-11
期刊：
Journal of Zhejiang University. Science B, Biomedicine & Biotechnology
影响因子：
--
作者：
Zhou Lisha;Dong Changsheng;Xu Zhuoming;Wang Xinran;Zhang Luyi;Chen Siyuan;Chen Jiahao;Zhu Yingying
通讯作者：
Zhu Yingying
影响因子：
28.2
作者：
Krishnamoorthy GP;Davidson NR;Leach SD;Zhao Z;Lowe SW;Lee G;Landa I;Nagarajah J;Saqcena M;Singh K;Wendel HG;Dogan S;Tamarapu PP;Blenis J;Ghossein RA;Knauf JA;Rätsch G;Fagin JA
通讯作者：
Fagin JA
人类 RNA 监视因子 UPF1 通过靶向长非编码 RNA MALAT1 来调节胃癌进展。
影响因子：
--
作者：
Li, Li;Geng, Yingying;Fei, Sujuan
通讯作者：
Fei, Sujuan