Int J Biol Sci 2022; 18(8):3313-3323. doi:10.7150/ijbs.72526 This issue

Research Paper

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

Teng-fei Chen1#, Hui-fei Hao2#, Yan Zhang3#, Xiao-yu Chen4, Hua-si Zhao1, Rui Yang1, Ping Li1, Ling-xiao Qiu1, Yong-hua Sang5✉, Chun Xu6✉, Shao-xia Liu1✉

1. Respiratory Department I, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
2. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong, China
3. Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China
4. Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
5. Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China
6. Department of Thoracic Surgery, Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
# Co-first author

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Citation:
Chen Tf, Hao Hf, Zhang Y, Chen Xy, Zhao Hs, Yang R, Li P, Qiu Lx, Sang Yh, Xu C, Liu Sx. HBO1 induces histone acetylation and is important for non-small cell lung cancer cell growth. Int J Biol Sci 2022; 18(8):3313-3323. doi:10.7150/ijbs.72526. Available from https://www.ijbs.com/v18p3313.htm

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Abstract

Graphic abstract

We examined the expression and the potential biological function of HBO1 in non-small cell lung cancer (NSCLC). TCGA and Oncomine databases showed that HBO1 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 (CCR2, MYLK, VEGFR2 and OCIAD2) 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.