Knockdown of mitochondrial threonyl-tRNA synthetase 2 inhibits lung adenocarcinoma cell proliferation and induces apoptosis.
Knockdown of mitochondrial threonyl-tRNA synthetase 2 inhibits lung adenocarcinoma cell proliferation and induces apoptosis.
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敲低线粒体苏氨酰-tRNA合成酶2抑制肺腺癌细胞增殖并诱导细胞凋亡
DOI：
10.1080/21655979.2022.2037368
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发表时间：
2022-03
期刊：
影响因子：
4.9
通讯作者：
Li R
中科院分区：
文献类型：
--
作者：
Tian H;Yan H;Zhang Y;Fu Q;Li C;He J;Li H;Zhou Y;Huang Y;Li R
摘要肺癌是一个重大的全球负担。氨酰-tRNA合成酶（aaRSs）可以通过肿瘤的发生和改善来可靠地鉴定。苏氨酰-tRNA合成酶（TARS）和线粒体苏氨酰-tRNA合成酶2（TARS 2）都是aaRS。许多研究表明，TARS参与肿瘤血管生成和转移。然而，TARS 2在肿瘤中尚未报道。本研究探讨了TARS 2在肺腺癌细胞增殖和凋亡中的作用。采用免疫组化法检测肺腺癌和非癌肺组织中TARS 2的表达。使用MTS、克隆形成和EdU染色测定检测细胞增殖。流式细胞仪检测细胞周期、线粒体活性氧（mROS）产生和细胞凋亡。用JC-1荧光探针检测线粒体膜电位（MMP Δ pM）。Western blotting检测细胞周期、凋亡相关通路及线粒体DNA编码蛋白的表达。最后，使用裸鼠中的异种移植肿瘤模型检查了TARS 2对肿瘤生长的影响。我们发现TARS 2在肺腺癌组织中高表达，并且与较差的总生存率（OS）相关。机制分析表明，敲低TARS 2通过视网膜母细胞瘤蛋白（RB）途径抑制增殖，并促进mROS诱导的凋亡。TARS 2的敲低抑制异种移植肿瘤模型中的肿瘤生长。TARS 2在LUAD细胞增殖和凋亡中起重要作用，可能成为一个新的治疗靶点。图形摘要
ABSTRACT Lung cancer is a significant global burden. Aminoacyl-tRNA synthetases (aaRSs) can be reliably identified by the occurrence and improvement of tumors. Threonyl-tRNA synthetase (TARS) and mitochondrial threonyl-tRNA synthetase 2 (TARS2) are both aaRSs. Many studies have shown that TARS are involved in tumor angiogenesis and metastasis. However, TARS2 has not yet been reported in tumors. This study explored the role of TARS2 in the proliferation and apoptosis of lung adenocarcinoma (LUAD). TARS2 expression in lung adenocarcinoma and non-cancerous lung tissues was detected via immunohistochemistry. Cell proliferation was detected using MTS, clone formation, and EdU staining assays. Flow cytometry was used to detect cell cycle, mitochondria reactive oxygen species (mROS) production, and apoptosis. Mitochondrial membrane potential (MMP ΔΨm) was detected using JC-1 fluorescent probes. Cell cycle, apoptosis-related pathway, and mitochondrial DNA (mtDNA) -encoded protein expression was detected via Western blotting. Finally, the effect of TARS2 on tumor growth was examined using a xenotransplanted tumor model in nude mice. We found that TARS2 was highly expressed in lung adenocarcinoma tissues and associated with poor overall survival (OS). Mechanistic analysis showed that knockdown of TARS2 inhibited proliferation through the retinoblastoma protein (RB) pathway and promoted mROS-induced apoptosis. Knockdown of TARS2 inhibits tumor growth in a xenotransplanted tumor model. TARS2 plays an important role in LUAD cell proliferation and apoptosis and may be a new therapeutic target. Graphical abstract
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影响因子：
56.9
作者：
Kampjut, Domen;Sazanov, Leonid A.
通讯作者：
Sazanov, Leonid A.
苏氨酰-tRNA 合成酶样蛋白具有 tRNA 氨酰化和编辑活性
影响因子：
14.9
作者：
Chen Y;Ruan ZR;Wang Y;Huang Q;Xue MQ;Zhou XL;Wang ED
通讯作者：
Wang ED
USP27 介导的细胞周期蛋白 E 稳定驱动细胞周期进展和肝细胞肿瘤发生
影响因子：
8
作者：
Dong L;Yu L;Bai C;Liu L;Long H;Shi L;Lin Z
通讯作者：
Lin Z
DOI：
10.1007/978-94-007-2869-1_7
发表时间：
2012-01-01
期刊：
ADVANCES IN MITOCHONDRIAL MEDICINE
影响因子：
--
作者：
Estaquier, Jerome;Vallette, Francois;Mignotte, Bernard
通讯作者：
Mignotte, Bernard
TELO2通过mTORC2与RICTOR结合诱导结直肠癌进展
影响因子：
4.2
作者：
Guo Z;Zhang X;Zhu H;Zhong N;Luo X;Zhang Y;Tu F;Zhong J;Wang X;He J;Huang L
通讯作者：
Huang L