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Author: Sophia
Reading guide:EBV-associated gastric cancer (EBVAGC) is considered a distinct molecular subtype of GC, accounting for approximately 9% of all GC cases. Clinically, it was found that the frequency of lymph node metastasis in EBVAGC patients was significantly lower than that in uninfected patients, and the prognosis was better. RNA N6-methyladenosine (M6A) modification has an integral role in regulating tumor progression in various cancer types. However, its effect on EBVAGC is unknown.
Recently, researchers from Sun Yat-sen University published a study entitled "FTO Up-regulation Induced by Myc Suppresses Tumour Progression in Epstein Barr Virus-associated Gastric Cancer" in the journal Clinical and Translational MedicineThis study revealed the significance of FTO-FOS-IGF2BP12 as a prospective biomarker combination for GC transfer** and elucidated the regulatory mechanism of EBVAGC transfer reduction from an epigenetic perspective.
Background:
Gastric cancer (GC) is the fifth most common malignancy worldwide and the fourth leading cause of cancer death. Taking into account the histological heterogeneity of GC, the Cancer Gene Profile (TCGA), which is divided into four subtypes based on molecular classification, one of which is a distinct molecular subtype, Epstein-U2012Barr virus-associated gastric cancer (EBVAGC), named for EBV infection in GC cells, which accounts for about 9% of all GC cases. EBV, also known as human herpes virus, is widespread in the population, with more than 90% of adults establishing a lifelong latent infection. EBVAGC belongs to latency I and latency II and constitutively expresses latent gene products such as EBV-encoded small RNA (EBER), EBV nuclear antigen 1 (EBNA1), and latent membrane protein 2a (LMP2A). In addition, EBVAGC typically exhibits molecular features such as PIK3CA mutations, DNA hypermethylation, and amplification of JAK2, PD-L1, and PD-L2 genes, and the clinicopathological features of EBVAGC are male dominance and proximal gastric susceptibility. More importantly, the incidence of lymph node metastasis in infected patients tends to be significantly lower than in EBV-negative GC (EBVNGC) patients, and the clinical prognosis is good. Therefore,Exploring the underlying mechanism of reduced frequency of GC metastasis after EBV infection will provide new targets for GC** and may benefit the prognosis of GC patients**.
Research Progress
Several studies have shown that EBVNGC has significantly stronger metastatic potential than EBVAGC. As mentioned above, FTO significantly inhibited EBVAGC metastasis in vitro and in vivo, but was expressed lower in EBVNGC cells. Notably, in EBVNGC cells, we found that ectopic expression of FTO inhibited cell migration, invasion, and wound healing rates (Figure 8A-D), while protein levels of EMT-marker genes were further increased after FTO depletion (Figure 8E). In addition, FOS knockdown is expected to successfully inhibit the migration ability of EBVNGC cells (Figure 8F,G). In short,These data suggest the presence of an FTO Fos M6A regulatory axis in EBVNGC, which may provide us with potential GC** and prognostic targets.
The FTO Fos M6A regulatory axis is also present in EBVNGC cells.
Findings:
In summary,Based on the tumor suppressive effect of aberrant M6A-modified FTO in EBVAGC and its downstream regulatory mechanism, we found that the FTO-Fos-IGF2BP1 2 signaling pathway delays malignant progression in an M6A-dependent manner. In addition, we found that MYC induces FTO expression in the setting of EBV infection, which is responsible for the lower metastasis rate in EBVAGC. In addition, the FTO-FOS-IGF2BP1 2-axis can be extended as a biomarker to all patients with GC, regardless of their EBV infection status, and detection of expression of this biomarker combination can lead to ** prognosis in GC patients. However, there are some limitations to our study. The regulatory model of FTO-fos-IGF2BP1 2-M6A is one of the mechanisms that explains the decline of EBVAGC transfer, and other potential downstream target genes of FTO need to be further validated. Overall, the FTO-Fos-IGF2BP1 2 pathway provides a promising ** strategy for GC patients, which we will focus on exploring in the future (Fig. 8H).
A working model of the basic mechanisms in this work.
References: Note: This article aims to introduce the progress of medical research and cannot be used as a reference for ** scheme. If you need health guidance, please visit a regular hospital.
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