BCAR1 promotes proliferation and cell growth in lung adenocarcinoma via upregulation of POLR2A

Autor: Qunyou Tan, Cheng Shen, Bo Deng, Chun-Guo Mao, Tan Long, Sha-Sha Jiang, Hua Jin
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Thoracic Cancer, Vol 11, Iss 11, Pp 3326-3336 (2020)
Thoracic Cancer
ISSN: 1759-7706
1759-7714
Popis: Background 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. Methods 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. Results 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. Conclusions 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.
Databáze: OpenAIRE
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