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WTAP promotes oesophageal squamous cell carcinoma development by decreasing CPSF4 expression in an m6A-dependent manner

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Abstract

m6A is a widespread RNA modification. However, the mechanism through which m6A regulated the progress of oesophageal squamous cell carcinoma (ESCC) remains undetermined. The levels and prognosis of WTAP were analysed using an ESCC tissue microarray (87 ESCC and 44 paracancerous tissues). TCGA and Oncolnc databases validate WTAP expression and prognosis. CCK8, colony formation (CF), wound healing, transwell cell invasion (CI), and migration (CM) assays were employed for the detection of the biological impacts of WTAP. Expression of tumour stemness-related genes was assessed via qRT-PCR and western blotting. The m6A RNA methylation (m6AMe) quantitative kit was employed for cellular methylation level detection. Arraystar m6A-mRNA and lncRNA epitranscriptomic microarray analyses were used to screen low methylation, high expression, and prognosis-related candidate gene CPSF4. KEGG enrichment analysis was used to screen the downstream signalling pathways of CPSF4. WTAP, a methyltransferase “writer”, was markedly enhanced in ESCC and was strongly correlated with poor patient outcome. WTAP knockdown inhibited the cell proliferation (CP), CI, CM, and stemness of ESCC cells in vitro and reduced the overall m6A modification (m6AMo) percentage of ESCC cells. CPSF4 is a target of WTAP-based m6AMo. WTAP-based m6AMo of CPSF4 transcript reduced the stability of CPSF4 by relying on YTHDF2. We identified the significant role of WTAP-catalysed m6AMo in ESCC tumourigenesis, wherein it facilitates ESCC tumour growth and metastasis through decreasing CPSF4 expression in an m6A-dependent manner.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China [Grant No. 31870352], 2021 Scientific Research Projects of the Health Commission of Anhui Province [Grant No. AHWJ2021b059], and 2021 Anhui Provincial Postgraduate Scientific Research Project of Universities [Grant No. YJS20210552].

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Author notes

  1. Qian Luo and Xuebing Zhan have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Pathology, Wannan Medical College, Wuhu, Anhui, China

    Qian Luo, Yunshu Kuang & Bing Chen

  2. Department of Pathology, The First People’s Hospital of Huizhou City, Huizhou, Guangdong, China

    Xuebing Zhan

  3. Graduate School, Wannan Medical College, Wuhu, Anhui, China

    Mingzhong Sun

  4. Department of Pathology, Maanshan People’s Hospital, Maanshan, Anhui, China

    Fangyuan Dong

  5. Department of Health Inspection and Quarantine, Wannan Medical College, Wuhu, Anhui, China

    Entao Sun

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  1. Qian Luo
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by QL, XZ, and YK. The first draft of the manuscript was written by QL and XZ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Entao Sun or Bing Chen.

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The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The organisation chip was approved by Shanghai Outdo Biotech Co., Ltd (Permission No.: SHYJS-CP-1807014).

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Luo, Q., Zhan, X., Kuang, Y. et al. WTAP promotes oesophageal squamous cell carcinoma development by decreasing CPSF4 expression in an m6A-dependent manner. Med Oncol 39, 231 (2022). https://doi.org/10.1007/s12032-022-01830-9

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