BAP18 Is Involved in Upregulation of CCND1/2 Transcription to Promote Cell Growth in Oral Squamous Cell Carcinoma

Abstract

Background: As a reader of histone H3K4me3, BPTF associated protein 18 kDa (BAP18) is a subunit of histone methyltransferase complex. BAP18 is involved in modulation of androgen receptor action in prostate cancer. However, the function of BAP18 on Oral squamous cell carcinoma (OSCC) and its molecular mechanism remains to be elusive. Methods: OSCC derived cell lines carrying silenced BAP18 were establish by Lentiviral vector transfection. RNA sequence analysis, quantitative RT-PCR, western blot, ChIP were performed to detect gene transcription regulation and the possible mechanism. Colony formation, cell growth curve and xenograft tumor experiments were performed to examine cell growth and proliferation. Findings: Our study demonstrated that BAP18 was highly expressed in OSCC samples compared with that in benign. BAP18 depletion obviously influenced the expression of a series of genes, involved in multiple biological processes. We thus provided the evidence to demonstrate that BAP18 depletion significantly decreases CCND1 and CCND2 (CCND1/2) transcription. In addition, BAP18 facilitated the recruitment of core subunits of MLL1/WDR5 complex to the promoter regions of CCND1/2, consequently increasing histone H3K4me3 levels. Furthermore, BAP18 depletion delayed G1-S phase transition and inhibited cell growth in OSCC derived cell lines. Interpretation: These study suggest that BAP18 involved in modulation of CCND1/2 transcription promotes OSCC progression and could be a potential therapeutic target for OSCC treatment. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China [31871286 for Yue Zhao, 81872015 for Chunyu Wang, 31701102 for Shengli Wang, 81702800 for Renlong Zou]; Foundation for Special Professor of Liaoning Province for Yue Zhao (the 5th batch). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Animal works were approved by the Animal Ethics Committee of China Medical University. The collection of tissue samples was approved by the Human Research Ethics Committee of China Medical University. All samples’ patient informed consents were already obtained.