HBO1 induces histone acetylation and is important for non-small cell lung cancer cell growth

• Published in: International journal of biological sciences Vol. 18; no. 8; pp. 3313 - 3323
• Main Authors: Chen, Teng-Fei, Hao, Hui-Fei, Zhang, Yan, Chen, Xiao-Yu, Zhao, Hua-Si, Yang, Rui, Li, Ping, Qiu, Ling-Xiao, Sang, Yong-Hua, Xu, Chun, Liu, Shao-Xia
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 2022; Ivyspring International Publisher
• Subjects: Acetylation; Animals; Anticancer properties; Antitumor agents; Bone cancer; Carcinoma, Non-Small-Cell Lung - genetics; CCR2 protein; Cell growth; Cell migration; Cell proliferation; Cell viability; CRISPR; Epigenetics; Gene expression; Genes; Histone Acetyltransferases - metabolism; Histones; Histones - genetics; Histones - metabolism; Humans; Lung cancer; Lung Neoplasms - genetics; Mice; Mice, Nude; Monocyte chemoattractant protein 1; Neoplasm Proteins - metabolism; Non-small cell lung carcinoma; Patients; Protein expression; Proteins; Research Paper; RNA, Small Interfering - genetics; Small cell lung carcinoma; Tissues; Tumors; Viruses; Xenografts; Xenotransplantation; China
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.72526

We examined the expression and the potential biological function of HBO1 in non-small cell lung cancer (NSCLC). TCGA and Oncomine databases showed that transcripts were elevated in NSCLC. Furthermore, in local NSCLC tumor tissues HBO1 expression was higher than that in matched adjacent lung tissues. In primary and immortalized NSCLC cells, HBO1 shRNA robustly inhibited cell viability, proliferation and migration. Moreover, HBO1 knockout by CRISPR/Cas9 induced significant anti-tumor activity in NSCLC cells. Conversely, ectopic HBO1 overexpression in primary NSCLC cells increased proliferation and migration. H3-H4 histone acetylation and expression of several potential oncogenic genes ( , , and ) were significantly decreased in NSCLC cells with HBO1 silencing or knockout. They were however increased after HBO1 overexpression. Intratumoral injection of HBO1 shRNA-expressing adeno-associated virus hindered the growth of A549 cell xenografts and primary NSCLC cell xenografts in nude mice. H3-H4 histone acetylation as well as expression of HBO1 and HBO1-dependent genes were decreased in HBO1-silenced NSCLC xenograft tissues. An HBO1 inhibitor WM-3835 potently inhibited NSCLC cell growth. Together, HBO1 overexpression promotes NSCLC cell growth.