Role of m6A methyltransferase component VIRMA in multiple human cancers (Review)

Abstract

N6-Methyladenosine (m6A) modification is one of the most widely distributed RNA modifications in eukaryotes. It participates in various RNA functions and plays vital roles in tissue development, stem cell formation and differentiation, heat shock response control, and circadian clock controlling, particularly during tumor development. The reversible regulation of m6A modification is affected by the so-called ‘reader’, ‘writer’ and ‘eraser’. As a required component and the largest methyltransferase, vir-like m6A methyltransferase associated (VIRMA) can promote the progression of cancer and is associated with poor survival in multiple types of cancer. The present review investigated the role of VIRMA in various types of cancer. In an m6A-dependent or -independent manner, VIRMA can play an oncogenic role by regulating cancer cell proliferation, migration and invasion, metastasis, apoptosis resistance and tumor growth in different pathways by targeting stem factors, CCAT1/2, ID2, GATA3, CDK1, c-Jun, etc. VIRMA can also predict better prognosis in kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP) and papillary thyroid carcinoma by TCGA analysis. The obvious oncogenic roles of VIRMA observed in different types of cancer and the mechanisms of VIRMA promoting cancers provided the basis for potential therapeutic targeting for cancer treatments.

The component of the m6A writer complex VIRMA is implicated in aggressive tumor phenotype, DNA damage response and cisplatin resistance in germ cell tumors

“…VIRMA has an oncogenic role in other tumor models [56][57][58][59][60], including urological malignancies [29]. Indeed, our previous observations highlighted frequent VIRMA upregulation in primary TGCTs (which was also confirmed in an independent study analyzing multiple cancer types [22]), with strong VIRMA immunoexpression found in 72.4% of samples and, in particular, in 84.2% of metastatic patient samples [3,10]. For those reasons, we aimed at a better understanding of the biological implications in TGCTs.…”

“…In a previous work, we have proven the relevance of VIRMA (also known as KIAA1429) in these tumors [10]. VIRMA (or vir-like m 6 A methyltransferase associated) is a critical part of the methyltransferase complex (which includes METTL3, the catalytic component, as well as other players such as WTAP and METTL14 that work together to stabilize and allow the functionality of the complex) and was shown to contribute to cancer progression in multiple malignancies by regulating cell cycle progression, migration, invasion, resistance to apoptosis and tumor growth, in both m 6 A dependent and independent manners [22]. In our cohort of 122 TGCT patients, VIRMA (and the m 6 A reader YTHDF3) was found to be significantly upregulated (at both transcript and protein levels) in SE compared to NS subtypes, confirming in silico data reporting these two m 6 A-related players as the most upregulated in TGCTs.…”

Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma

“…In endometrial cancer, it was reported to be downregulated and to modulate the expression of members of the AKT pathway and inhibit cell proliferation ( Cai et al, 2018 ; Visvanathan et al, 2018 ; Miao et al, 2019 ; Peng et al, 2019 ; Li et al, 2020 ; Liang et al, 2020 ; Nombela et al, 2021 ). KIAA1429 was reviewed to be upregulated in 12 types of cancers and to be downregulated in 4 cancer types ( Zhu et al, 2021 ). METTL16 was found to be overexpressed in colorectal cancer and to be underexpressed in hepatocellular carcinoma, affecting activation of multiple metabolic pathways ( Liu et al, 2019 ; Wang et al, 2020 ).…”

A Risk Score Model Incorporating Three m6A RNA Methylation Regulators and a Related Network of miRNAs-m6A Regulators-m6A Target Genes to Predict the Prognosis of Patients With Ovarian Cancer

“…Among these regulators, vir-like m6A methyltransferase associated (VIRMA), a “writer” of m6A regulators, promotes the progression of cancer and is associated with shorter survival for patients with multiple types of cancer, such as kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, and papillary thyroid carcinoma ( Zhu et al, 2021 ). However, no reports have examined the correlation between VIRMA expression and OC progression.…”