Upregulation of OATP1A2 in human oesophageal squamous cell carcinoma cells via the HDAC6-GCN5/PCAF-H3K9Ac axis

Abstract

1. OATP1A2 overexpressed is involved in chemotherapy disposition, indicating its role in tumour development and progression.

2. CHIP and siRNA were used to evaluate the status of histone acetylation at the OATP1A2 promoter. The role of OATP1A2 was analysed by gene-set enrichment and overall survival analysis.

3. OATP1A2 expression levels in ESCC was notably higher than that in para-cancer tissues. OATP1A2 high expression are associated with bile salt metabolic pathway and poor prognosis. Furthermore, HDAC6 was repressed in ESCC, increasing the levels of H3K9Ac catalysed by GCN5/PCAF at the OATP1A2 promoter region.

4. Abnormal histone hyperacetylation mediated by the HDAC6-GCN5/PCAF-H3K9Ac axis resulted in increased OATP1A2 expression in ESCC, and OATP1A2 may serve as a promising prognostic biomarker for ESCC.

5. In conclusion, this study indicated that suppression of OATP1A2 would inhibit the progression and prognosis in ESCC.

Keywords:

• Histone acetylation
• OATP1A2
• ESCC
• GCN5/PCAF

Ethical approval

All specimens were collected by surgical resection from Hangzhou Cancer Hospital with the written informed consent provided by the patients and the approval by the Institutional Review Board of Hangzhou Cancer Hospital (Permit Number: HZCH-2016-02). Patients had provided informed consent for the use of their tissue samples and clinical data for research purposes. Written informed consent for publication was obtained from all participants.

Acknowledgements

The authors thank Hangzhou Cancer Hospital for providing us with the pathological tissues and adopting the ethics. Our thanks to all participants who consented to take part in this trial.

Author contributions

Designed and supervised the study: Lvhua Wang and Su Zeng. Performed most of the experiments and wrote the manuscript: Xiaoli Zheng and Jian V. Zhang. Conducted IHC experiment and analysis: Yanfeng Bai. Conducted western blotting and qRT-PCR experiments and analysis: Jiaqi Wang. Wrote and revised a part of the manuscript Lvhua Wang and Mingfeng Jiang.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available in the supplementary material of this article. All data generated or analysed in the current study are included in this publication and are available on reasonable request.

Additional information

Funding

This work was financially supported by National Natural Science Foundation of China [No. 81702801], China Postdoctoral Science Foundation [No. 2020M680130], Sanming Project of Medicine in Shenzhen [No. SZSM201612063], Zhejiang Provincial Natural Sciences Foundation of China [No. LGF19H310001].