AUTHOR=Wang Kai , Zhang Man , Wang Jiao , Sun Pan , Luo Jizhuang , Jin Haizhen , Li Rong , Pan Changqing , Lu Liming 

TITLE=A Systematic Analysis Identifies Key Regulators Involved in Cell Proliferation and Potential Drugs for the Treatment of Human Lung Adenocarcinoma

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.737152

DOI=10.3389/fonc.2021.737152

ISSN=2234-943X

ABSTRACT=<p>Lung adenocarcinoma (LUAD) is one of the most common and malignant cancer types. Abnormal cell proliferation, exemplified by cell cycle and cell division dysregulation, is one of the most prominent hallmarks of cancer and is responsible for recurrence, metastasis, and resistance to cancer therapy. However, LUAD-specific gene regulation and clinical significance remain obscure. Here, by using both tissues and cells from LUAD and normal lung samples, 434 increased and 828 decreased genes of biological significance were detected, including 127 cell cycle-associated genes (95 increased and 32 decreased), 66 cell division-associated genes (56 increased and 10 decreased), and 81 cell proliferation-associated genes (34 increased and 47 decreased). Among them, 12 increased genes (<italic>TPX2</italic>, <italic>CENPF</italic>, <italic>BUB1</italic>, <italic>PLK1</italic>, <italic>KIF2C</italic>, <italic>AURKB</italic>, <italic>CDKN3</italic>, <italic>BUB1B</italic>, <italic>HMGA2</italic>, <italic>CDK1</italic>, <italic>ASPM</italic>, and <italic>CKS1B</italic>) and 2 decreased genes (<italic>TACC1</italic> and <italic>MYH10</italic>) were associated with all the three above processes. Importantly, 2 (<italic>CDKN3</italic> and <italic>CKS1B</italic>) out of the 11 increased genes (except <italic>HMGA2</italic>) are previously uncharacterized ones in LUAD and can potentially be prognostic markers. Moreover, <italic>PLK1</italic> could be a promising therapeutic target for LUAD. Besides, protein–protein interaction network analysis showed that <italic>CDK1</italic> and <italic>CDC20</italic> were the hub genes, which might play crucial roles in cell proliferation of LUAD. Furthermore, transcriptional regulatory network analysis suggested that the transcription factor E2F1 could be a key regulator in controlling cell proliferation of LUAD <italic>via</italic> expression modulation of most cell cycle-, cell division-, and cell proliferation-related DEGs. Finally, trichostatin A, hycanthone, vorinostat, and mebeverine were identified as four potential therapeutic agents for LUAD. This work revealed key regulators contributing to cell proliferation in human LUAD and identified four potential therapeutic agents for treatment strategy.</p>