The m6A methyltransferase METTL3 affects autophagy and progression of nasopharyngeal carcinoma by regulating the stability of lncRNA ZFAS1

Abstract

Background Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the epithelial cells of the nasopharyngeal mucosa of the head and neck. The role of long non-coding RNA and RNA methylation in NPC has received increasing attention. Therefore, this study aims to investigate the mechanism of lncRNA ZFAS1 in NPC and its relationship with RNA methylation, providing evidence for targeted therapy of NPC. Methods Microarray arrays were used to screen the differentially expressed miRNAs in normal tissues and tumor tissues. QRT-PCR was used to quantify ZFAS1, miR-100-3p, ATG10, autophagy and epithelial-mesenchymal transition related genes. The interactive relationship between ZFAS1 and miR-100-3p was verified using dual-luciferase reporter gene assay and RIP assay. CCK-8, transwell and apoptosis were used to detect the occurrence of tumor cells after different treatments. The m6A modification test is used to verify the effect of METTL3 on ZFAS1. BALB/c mice and BALB/c nude mice are used to detect the effects of different treatments on tumor growth and immune escape in vivo. Results ZFAS1 is upregulated in tumor tissues and NPC cells. N (6)-methyladenosine (m6A) is highly enriched in ZFAS1 and enhances its RNA stability. ZFAS1 is used as an oncogenic lncRNA, which can promote NPC cell proliferation, migration and tumor growth. In terms of mechanism, ZFAS1 up-regulates the expression of ATG10 by competitively adsorbing miR-100-3p and regulates the level of autophagy by inhibiting the PI3K/Akt signaling pathway to promote the proliferation and migration of NPC cells. Conclusion In short, our study verified the cancer-promoting effect of ZFAS1 in NPC and explained part of the reason for its upregulation. In addition, we confirmed that ZFAS1 can regulate the autophagy level of NPC cells through the PI3K/AKT pathway through miR-100-3p/ATG10 to affect tumor progression.

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

“…A study revealed that the m6A reader YTHDC1 blocked ubiquitination between lncRNA LSG1 and ESRP2 and inhibited the advancement of renal cell carcinoma [ 32 ]. By altering the stability of lncRNA ZFAS1, the m6A methyltransferase METTL3 influenced autophagy and the development of nasopharyngeal cancer cells [ 33 ]. Bioinformatics studies have also indicated the prognostic characteristics of m6A-related lncRNAs in gastric cancer [ 34 , 35 ].…”

N6-Methyladenosine RNA Modification Landscape in the Occurrence and Recurrence of Nasopharyngeal Carcinoma

“…Insulin like growth factor binding protein 1 (IGFBP1), an important molecule of m6A, has also been shown to promote cell proliferation and metastasis in NPC driven by Myc [15], and WTAP promotes DIAPH1-AS1 can promote the proliferation and invasion of NPC [16]. METTL3 can also promote the development of NPC by promoting the stability of ZFAS1 [17]. circMAP3K4 promotes the development of NPC by regulating its ability to encode small peptides through regulating m6A modification [18].…”

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

“…YTHDF2 captured eIF4G1 transcripts containing m6A and induced mRNA degradation, thereby promoting autophagy and reducing tumor occurrence [ 147 ]. m6A modification enhanced the stability of ZFAS1 [ 148 ]. Lnc RNA ZFAS1 is upregulated in tumor tissues and neural progenitor cells (NPC) [ 148 ].…”

“…m6A modification enhanced the stability of ZFAS1 [ 148 ]. Lnc RNA ZFAS1 is upregulated in tumor tissues and neural progenitor cells (NPC) [ 148 ]. ZFAS1 upregulated the expression of ATG10 and regulated autophagy by inhibiting the PI3K/Akt signaling pathway to promote the proliferation and migration of NPC cells [ 148 ].…”