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Abstract N6-methyladenosine (m6A) methylation, as a new regulatory mechanism, has been reported to be involved in diverse biological processes in recent years. Wilms tumor 1-associated protein (WTAP), as the key member of m6A methylation, has been proved to participate in the tumorigenesis. Here, we studied the expression of WTAP and its potential mechanism involved in the development of esophageal squamous cell carcinoma (ESCC). We detected the expression of WTAP and its correlation with clinicopathological features, and we determined the function of WTAP on ESCC cells by MTS assay, colony formation, scratch wound healing assay, transwell assays and subcutaneous xenograft assay. We used mRNA sequencing technology to screen candidate downstream targets for WTAP, and investigated the underlying mechanism of CCND1 in ESCC promotion through a series of rescue assays. An elevated expression of WTAP in ESCC malignancy indicated a worse prognosis. WTAP promoted proliferation and metastasis of ESCC cells and CCND1 was identified as the potential downstream effecter of WTAP. Moreover, WTAP modulated ESCC progression through MAPK pathway-dependent pattern. Our research suggested that WTAP promoted both proliferation and metastasis of ESCC by accelerating the expression of CCND1 via MAPK signaling pathway, indicating that WTAP may be a candidate prognostic biomarker for ESCC and also will be a promising strategy for ESCC cancer therapy.
Zhang et al. (Thu,) studied this question.