FTO‐mediated ZNF687 accelerates tumor growth, metastasis, and angiogenesis in colorectal cancer through the Wnt/β‐catenin pathway

Abstract

AbstractColorectal cancer (CRC) is a common and lethal cancer. ZNF687 has been disclosed to take part in diversified cancers’ progression by serving as a facilitator. However, the detailed regulatory functions of ZNF687 in the CRC have not been investigated. This work is planned to probe the impacts of ZNF687 on CRC progression. The IHC, RT‐qPCR, and western blot assays were used to examine mRNA and protein gene expressions. The cell proliferation measurement was accompanied by a CCK‐8 assay. The Transwell assay was performed to evaluate cell invasion and migration. The angiogenesis ability was evaluated by a tube formation experiment. The m6A level was evaluated through MeRIP and m6A dot blot assays. The binding ability between ZNF687 and FTO (fat mass and obesity associated protein) was tested through an RIP assay. The β‐catenin nuclear translocation was assessed through an immunofluorescence assay. The tumor growth was evaluated through an in vivo assay. ZNF687 exhibited higher expression in CRC cells and resulted in a poor prognosis. Additionally, ZNF687 inhibition suppressed CRC cell proliferation, invasion, migration, and angiogenesis. Furthermore, the suppression of ZNF687 retarded the Wnt pathway. Through rescue assays, the reduced cell migration, proliferation, invasion, and angiogenesis mediated by ZNF687 knockdown could be reversed after BML‐284 (the activator of the Wnt pathway) treatment. Finally, it was explained that ZNF687 knockdown inhibited in vivo tumor growth. This study manifested that FTO‐mediated ZNF687 aggravated tumor growth, metastasis, and angiogenesis of CRC through Wnt/β‐catenin pathway. This finding may provide a hopeful molecular target for CRC treatment.