RETRACTED: YTHDF1 Facilitates the Progression of Hepatocellular Carcinoma by Promoting FZD5 mRNA Translation in an m6A-Dependent Manner

Abstract

Hepatocellular carcinoma (HCC), one of the most aggressive malignancies, ranks as the fourth leading cause of cancerrelated deaths worldwide. Emerging evidence indicates that RNA N6-methyladenosine (m6A) plays a critical role in tumor progression. However, the biological function of YTHDF1 in HCC remains unclear. Here, we found that YTHDF1 expression was strikingly elevated in HCC tissues and cell lines and significantly associated with prognosis of HCC patients. Moreover, YTHDF1 expression was transcriptionally regulated by USF1 and c-MYC in HCC. Functional studies showed that YTHDF1 can promote HCC cell proliferation and metastasis both in vitro and in vivo. Multi-omics analysis revealed that YTHDF1 can accelerate the translational output of FZD5 mRNA in an m6A-dependent manner and function as an oncogene through the WNT/b-catenin pathway. Taken together, our study revealed an essential role of YTHDF1 in the progression of HCC cells, which indicated that targeting YTHDF1 may be a potential therapeutic strategy in HCC.

Analysis and Validation of circRNA-miRNA Network in Regulating m6A RNA Methylation Modulators Reveals CircMAP2K4/miR-139-5p/YTHDF1 Axis Involving the Proliferation of Hepatocellular Carcinoma

“…YTHDF1 high expression was correlated with high pathological grade and advanced stage, which indicates YTHDF1 may be involved in the migration and metastasis of HCC. Indeed, previous studies have confirmed that upregulation of YTHDF1 improve the migratory and invasive capabilities of HCC cells ( 30 , 31 ), which provide clues for the investigation of circMAP2K4/miR-139-5p/YTHDF1 axis in the migration and metastasis of HCC in our future study.…”

“…As an m 6 A reader, YTHDF is also involved in the occurrence of HCC. YTHDF1 promotes HCC progression by enhancing FZD5 mRNA translation or AKT/GSK-3β/β-catenin signaling activation ( 30 , 31 ). YTHDF2 is involved in the decay of IL11 and Serpine2 mRNA, which are important genes that regulate the normalization and inflammation of vessels ( 32 ).…”

The m6A Reader YTHDF1 Facilitates the Tumorigenesis and Metastasis of Gastric Cancer via USP14 Translation in an m6A-Dependent Manner

“…Tumor growth and invasion can be effectively controlled by m 6 A-related “writers,” “readers,” and “erasers,” which determine the fate of m 6 A-modified mRNAs ( Lin et al, 2016 ; Ma et al, 2017 ; Li N. et al, 2020 ; Wang et al, 2020 ). Higher expression of YTHDF1 is related to worse prognosis in patients with hepatocellular carcinoma ( Liu X. et al, 2020 ). We herein found that YTHDF1 as a m 6 A “reader” was upregulated in GC tissues.…”

“…METTL3 enhances metastasis of GC by m 6 A modification of ZMYM1/E-cadherin signaling, and WTAP results in a poor clinical prognosis of GC through regulating tumor-related immune infiltration ( Yue et al, 2019 ; Li H. et al, 2020 ). YTHDF1 (m 6 A “reader”) can be used to predict poor prognosis in breast cancer and promotes FDZ5 translation, leading to hepatocellular carcinoma progression ( Anita et al, 2020 ; Liu X. et al, 2020 ). YTHDF1 can bind to mammalian mRNAs and alter the protein translation process in a m 6 A-dependent manner.…”

Dynamic Expression of m6A Regulators During Multiple Human Tissue Development and Cancers

“…Xu et al found that 19 m 6 A regulators were highly expressed in glioma tissues, and the expression of regulators was associated with prognoses and grade (Xu et al, 2020b ). One recent study has revealed an essential role of YTHDF1 in the progression of hepatocellular carcinoma (Liu et al, 2020 ). RNA methyltransferase METTL3 has been found to facilitate colorectal cancer by activating m6A-GLUT1-mTORC1 axis and is a therapeutic target (Chen et al, 2020 ).…”