Methyltransferase-like 3 induces the development of cervical cancer by enhancing insulin-like growth factor 2 mRNA-binding proteins 3-mediated apoptotic chromatin condensation inducer 1 mRNA stability

Abstract

N6-methyladenosine (m6A) plays a critical role in the tumorigenesis of cervical cancer (CC). Here, we aimed to investigate the potential role of methyltransferase-like 3 (METTL3) in CC. Gene expression was determined via real-time quantitative polymerase chain reaction. Cellular functions were detected using colony formation, 5-ethynyl-2′-deoxyuridine (EdU), and Transwell assays. The interactions among METTL3, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), and apoptotic chromatin condensation inducer 1 (ACIN1) were confirmed using the MeRIP and RIP assays. An in vivo assay was performed to verify the role of METTL3 in CC development. METTL3 is overexpressed in CC, and therefore, its knockdown inhibits the proliferation and migration of CC cells. Silencing METTL3 inhibits tumor growth in vivo . Moreover, a positive association was observed between METTL3 and ACIN1. METTL3 interacts with IGF2BP3 to promote the mRNA stability of ACIN1, the overexpression of which induces the aggressiveness of CC cells. METTL3 promotes ACIN1 mRNA stability to accelerate CC progression, implying that METTL3 is a promising biomarker in CC.

Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential

“…In colon cancer, IGF2BP3 boosts DNA replication and cell proliferation by binding to m 6 A-modified sites in CCND1 mRNA and preventing its degradation [ 56 ]. ACIN1 is stabilized through METTL3/IGF2BP3, boosting proliferation and migration of cervical cancer cells [ 57 ]. In hepatocellular carcinoma, lnc-CTHCC, stabilized by METTL3/IGF2BP1/IGF2BP3 via m 6 A modification, promotes tumor initiation and development by binding hnRNPK and activating YAP1 transcription [ 58 ].…”

METTL3's role in cervical cancer development through m6A modification

“…METTL3 could promote the occurrence and development of CC through IGF2BP3. 29 Additionally, METTL3 promotes CC progression by inhibiting endoplasmic reticulum stress through the m 6 A modification of TXNDC5 mRNA. 30 However, the specific mechanism of m 6 A action in CC remains unknown, given the diverse range of its functions.…”

The role of RNA methyltransferase METTL3 in gynecologic cancers: Results and mechanisms

“…Its overexpression inhibits the proliferation and migration ability of CC cells and enhances the apoptosis rate ( Ji et al, 2021 ). In addition, Mettl3 synergizes with IGF2BP3 to extend the half-life of ACIN1 and RAB2B mRNA to contribute to the growth of CC and poor prognosis ( Hu et al, 2020 ; Su et al, 2022 ). Recent research has revealed that Mettl3 is highly expressed in CC cells in the M stage, increases m6A methylation of CDC25B mRNA, and enhances its translation activity by recruiting YTHDF-1.…”