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H3K27me3 Inactivates SFRP1 to Promote Cell Proliferation via Wnt/β-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma

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Abstract

Background

Histone methylations are generally considered to play an important role in multiple cancers by regulating cancer-related genes.

Aims

This study aims to investigate the effects of H3K27me3-mediated inactivation of tumor suppressor gene SFRP1 and its function in esophageal squamous cell carcinoma (ESCC).

Methods

We performed ChIP-seq on H3K27me3-enriched genomic DNA fragments in ESCC cells to screen out tumor suppressor genes that may be regulated by H3K27me3. ChIP-qPCR and Western blot were employed to explore the regulating mechanisms between H3K27me3 and SFRP1. Expression level of SFRP1 was assessed by quantitative real-time polymerase chain reaction (q-PCR) in 29 pairs of ESCC surgical samples. SFRP1 function in ESCC cells were detected by cell proliferation assay, colony formation assay and wound-healing assay.

Results

Our results indicated that H3K27me3 was widely distributed in the genome of ESCC cells. Specifically, we found that H3K27me3 deposited on the upstream region of SFRP1 promoter and inactivated SFRP1 expression. Furthermore, we found SFRP1 was significantly down-regulated in ESCC tissues compared with the adjacent non-tumor tissues, and SFRP1 expression was significantly associated with TNM stage and lymph node metastasis. In vitro cell-based assay indicated that over-expression of SFRP1 significantly suppressed cell proliferation and negatively correlated with the expression of β-catenin in the nucleus.

Conclusions

Our study revealed a previously unrecognized finding that H3K27me3-mediated SFRP1 inhibit the cell proliferation of ESCC through inactivation of Wnt/β-catenin signaling pathway.

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Funding

This research was supported by the Open Project Program of the Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, China (Grant No. LDGHD202102).

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Authors and Affiliations

  1. Department of Medical Genetics and Developmental Biology, Medical School of Southeast University, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing, 210000, China

    Menghan Zhou, Yue Liu & Hong Fan

  2. School of Life Science and Technology, Southeast University, Nanjing, 210000, China

    Shenling Yu, Shihui Shu, Ying Xu, Min Liu & Yanping Ge

Authors
  1. Menghan Zhou
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  2. Shenling Yu
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  3. Yue Liu
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  4. Shihui Shu
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  6. Min Liu
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  7. Yanping Ge
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  8. Hong Fan
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Contributions

MZ: Formal analysis, Funding acquisition, Resources, Writing—original draft, Writing—review & editing. SY: Data curation, Investigation, Methodology. YL: Validation. SS: Data curation. YX: Software. ML: Validation. YG: Visualization. HF: Conceptualization, Project administration, Supervision.

Corresponding author

Correspondence to Hong Fan.

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Zhou, M., Yu, S., Liu, Y. et al. H3K27me3 Inactivates SFRP1 to Promote Cell Proliferation via Wnt/β-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma. Dig Dis Sci 68, 2463–2473 (2023). https://doi.org/10.1007/s10620-023-07892-7

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  • DOI: https://doi.org/10.1007/s10620-023-07892-7

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