ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2022; 13(3):906-917. doi:10.7150/jca.66404 This issue Cite
Research Paper
TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK
1. Center of Excellence for Environmental Safety and Biological Effects, Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China.
2. Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.
Abstract
Background: FAM110A belongs to the FAM110 family, which mainly functions in biological processes associated with the cell cycle. However, the biological functions in which FAM110A participates are largely undefined. In particular, its potential role in cancer remains unknown. The goal of this study was to uncover the role and mechanism of FAM110A in pancreatic cancer.
Methods: Based on bioinformatics databases, qPCR and Western blot assays, we verified the elevated expression level of FAM110A in PDAC. Subsequently, FAM110A, HIST1H2BK and TSPAN1 overexpression or knockdown stable transfected cells were employed for biological functions' studies to explore the role in PDAC in vitro and in vivo. RNA-Seq, Western blot and luciferase-reporter assays were used to explore mechanism of FAM110A action in PDAC, and the involved pathway was verified by tumor phenotypic rescue experiments.
Results: In this study, we demonstrated for the first time that FAM110A is an oncogene that promotes cell proliferation, migration, invasion and tumorigenesis in pancreatic cancer. HIST1H2BK was identified as the downstream target of FAM110A, while the promotion effect caused by FAM110A overexpression could be abolished by HIST1H2BK knockdown. Moreover, for the first time, we revealed the oncogenic role of HIST1H2BK in pancreatic cancer, and the tumor-promoting capacity of HIST1H2BK may be associated with its regulatory effect on G9a. In addition, we demonstrated that TSPAN1 displayed a positive transcriptional regulatory effect on FAM110A.
Conclusions: Collectively, FAM110A plays an oncogenic role in PDAC, and the newly identified TSPAN1/FAM110A/HIST1H2BK/G9a pathway is involved in the modulation of pancreatic cancer progression and provides a novel prognostic and therapeutic strategy for pancreatic cancer treatment.
Keywords: Pancreatic cancer, FAM110A, HIST1H2BK, TSPAN1, G9a
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