BCAR1 promotes proliferation and cell growth in lung adenocarcinoma via upregulation of POLR2A.
BCAR1 promotes proliferation and cell growth in lung adenocarcinoma via upregulation of POLR2A.
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DOI：
10.1111/1759-7714.13676
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发表时间：
2020-11
期刊：
影响因子：
2.9
通讯作者：
Deng B
中科院分区：
文献类型：
--
作者：
Mao CG;Jiang SS;Shen C;Long T;Jin H;Tan QY;Deng B
本研究旨在探讨一种新的致癌分子p130 cas（乳腺癌抗雌激素抵抗蛋白1或BCAR 1）对肺腺癌细胞增殖和生长的影响。该研究还旨在确定BCAR 1可能的潜在信号网络。首先，我们使用CRISPR-Cas9技术在H1975和H1299人肺腺癌细胞中评估了BCAR 1敲除（KO）后的增殖、细胞集落形成、细胞凋亡和细胞周期。随后，BCAR 1在293 T细胞中上调，免疫沉淀-质谱（IP-MS）与生物信息学分析一起用于筛选BCAR 1相互作用蛋白的潜在网络。最终，我们验证了BCAR 1和选定的枢纽基因RNA聚合酶II亚基A（POLR 2A）在54个肺腺癌组织以及H1975和H1299细胞中的相关表达。BCAR 1-KO后，H1975和H1299的细胞增殖受到显著抑制。在BCAR 1-KO后，H1975细胞的集落形成也显著减少。IP-MS证实了419种可能与BCAR 1相互作用的潜在蛋白质。经TCGA验证，其中68个基因与BCAR 1表达显著正相关。PPI String分析显示了6个枢纽基因。POLR 2A、MAPK 3、MOV 10和XAB 2的高表达预测肺腺癌的不良预后，如K-M数据库所证实的。POLR 2A和MAPK 3参与催化活性和转移酶活性。POLR 2A和BCAR 1在肺癌组织中的表达显著高于正常组织。POLR 2A的高表达与BCAR 1的过表达呈显著正相关，并预示54例肺癌患者的预后不良。在H1975和H1299细胞中，BCAR 1-KO后POLR 2A表达显著降低。BCAR 1促进增殖和细胞生长，可能是通过上调POLR 2A和随后的催化和转移酶活性的增强。然而，需要更多的可靠研究来阐明所涉及的机制。本研究旨在阐明一种新的致癌分子p130 cas（breast cancer antiestrogen resistance 1，BCAR 1）对肺癌细胞增殖和生长的促进作用，并探讨BCAR 1相互作用蛋白的可能网络。我们发现BCAR 1可以促进细胞增殖和生长，可能是通过上调POLR 2A和随后的催化活性和转移酶活性的增强。
This study was designed to investigate the effects of a novel carcinogenetic molecule, p130cas (breast cancer antiestrogen resistance protein 1 or BCAR1) on proliferation and cell growth in lung adenocarcinoma. The study also aimed to identify the possible underlying signal networks of BCAR1. First, we evaluated proliferation, cell colony formation, apoptosis, and cell cycle after BCAR1 was knocked out (KO) using CRISPR‐Cas9 technology in H1975 and H1299 human lung adenocarcinoma cells. Subsequently, BCAR1 was upregulated in 293T cells and immunoprecipitation‐mass spectrometry (IP‐MS) was used with bioinformatics analysis to screen for potential networks of BCAR1 interacting proteins. Ultimately, we validated the correlated expressions of BCAR1 and a selected hub gene, RNA polymerase II subunit A (POLR2A), in 54 lung adenocarcinoma tissues, as well as in H1975 and H1299 cells. Cell proliferation of H1975 and H1299 was significantly inhibited following BCAR1‐KO. Colony formation of H1975 cells was also significantly decreased following BCAR1‐KO. IP‐MS demonstrated 419 potential proteins that may interact with BCAR1. Among them, 68 genes were significantly positively correlated to BCAR1 expression, as verified by TCGA. Six hub genes were revealed by PPI String. High expression of POLR2A, MAPK3, MOV10, and XAB2 predicted poor prognosis in lung adenocarcinoma, as verified by the K‐M plotter database. POLR2A and MAPK3 are involved in both catalytic activity and transferase activity. POLR2A and BCAR1 were significantly increased in lung cancer tissues as compared with matched normal tissues. High expression of POLR2A was significantly positively correlated to BCAR1 overexpression and predicted poor prognosis in 54 lung cancer cases. POLR2A expression was significantly decreased following BCAR1‐KO in H1975 and H1299 cells. BCAR1 promotes proliferation and cell growth, probably via upregulation of POLR2A and subsequent enhancement of catalytic and transferase activities. However, additional robust studies are required to elucidate the mechanisms involved. In this work, we elaborated the enhancement effect of a novel carcinogenetic molecule, ie, p130cas (breast cancer antiestrogen resistance 1, BCAR1) on proliferation and cell growth of lung cancer cells,and to explore the possible networks of interacting proteins of BCAR1. We found BCAR1 can promote proliferation and cell growth, probably via upregulation of POLR2A and subsequent enhancement of catalytic activity and transferase activity.
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影响因子：
28.2
作者：
Rai K;Akdemir KC;Kwong LN;Fiziev P;Wu CJ;Keung EZ;Sharma S;Samant NS;Williams M;Axelrad JB;Shah A;Yang D;Grimm EA;Barton MC;Milton DR;Heffernan TP;Horner JW;Ekmekcioglu S;Lazar AJ;Ernst J;Chin L
通讯作者：
Chin L
BCAR1 增加预示多中心患者非小细胞肺癌的不良预后
影响因子：
3.7
作者：
Deng B;Sun Z;Jason W;Yang P
通讯作者：
Yang P
影响因子：
3.7
作者：
Camacho Leal Mdel P;Pincini A;Tornillo G;Fiorito E;Bisaro B;Di Luca E;Turco E;Defilippi P;Cabodi S
通讯作者：
Cabodi S
影响因子：
6.6
作者：
Gemperle, Jakub;Dibus, Michal;Brabek, Jan
通讯作者：
Brabek, Jan
影响因子：
6.6
作者：
Siebring-van Olst E;Blijlevens M;de Menezes RX;van der Meulen-Muileman IH;Smit EF;van Beusechem VW
通讯作者：
van Beusechem VW