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. 2022 Sep 29;39(12):231.
doi: 10.1007/s12032-022-01830-9.

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

Qian Luo #  1 , Xuebing Zhan #  2 , Yunshu Kuang  1 , Mingzhong Sun  3 , Fangyuan Dong  4 , Entao Sun  5 , Bing Chen  6
Affiliations

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

Qian Luo et al. Med Oncol. .

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.

Keywords: CPSF4; N6-methyladenosine; Oesophageal squamous cell carcinoma; WTAP.

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