MTFR2, A Potential Biomarker for Prognosis and Immune Infiltrates, Promotes Progression of Gastric Cancer Based on Bioinformatics Analysis and Experiments

Abstract

Background: Mitochondrial fission regulator 2 (MTFR2) which can promote mitochondrial fission, has recently been reported to be involved in tumorigenesis. However, little is known about its expression levels and function in gastric cancer (GC). This study aims to clarify the role of MTFR2 in GC. Methods:We firstly determined the expression level and prognostic value of MTFR2 in GC by integrated bioinformatics (Oncomine, GEPIA, Kaplan-Meier Plotter database) and experimental approaches (RT-qPCR, western blot, immunohistochemistry). After constructing stable down-regulated GC cells, the biological functions of MTFR2 in vitro and in vivo were studied through cell clone formation, wound healing, transwell and tumor formation experiments.To understand the reason for the high expression of MTFR2 in GC, copy number alternation, promoter methylation and mutation of MTFR2 were detected by UALCAN and cBioPortal. TargetScanHuman and PROMO databases were also used to explore the miRNAs and transcription factors of MTFR2, and the regulatory network was visualized by Cytoscape. LinkedOmics was used to detect the co-expression profile, and then these co-expressed genes were used for gene oncology function and pathway enrichment analysis to deepen the understanding of MTFR2 mechanism. The protein interaction network of MTFR2 was constructed by the GeneMANIA platform. Docking study of the binding mode was conducted by H DOCK webserver, and PYMOL is used for visualization, and analysis. TIMER database was used to explore the correlation between MTFR2 expression level and immune cells infiltration and gene markers of tumor infiltrating immune cells. Results: We demonstrated that MTFR2 was up-regulated in GC, and its overexpression led to poorer prognosis. MTFR2 downregulation inhibited the proliferation, migration, and invasion of GC cells in vitro and in vivo. By bioinformatics analysis, we identified the possible factors in MTFR2 overexpression. Moreover, function and pathway enrichment analyses found that MTFR2 was involved in chromosome segregation, catalytic activity, cell cycle, and ribonucleic acid transport. A MTFR2-protein interaction network revealed a potential direct protein interaction between MTFR2 and protein kinase adenosine-monophosphate-activated catalytic subunit alpha 1 (PRKAA1), and their potential binding site was predicted in a molecular docking model. In addition, we also found that MTFR2 may be correlated with immune infiltration in GC. Conclusions: Our study has effectively revealed the expression, prognostic value, potential functional networks, protein interactions and immune infiltration of MTFR2 in GC. Altogether, our data identify the possible underlying mechanisms of MTFR2 and suggest that MTFR2 may be a prognostic biomarker and therapeutic target in GC.

Negatively Regulated by miR-29c-3p, MTFR1 Promotes the Progression and Glycolysis in Lung Adenocarcinoma via the AMPK/mTOR Signalling Pathway

“…The disruption of this balance may contribute to the occurrence of different diseases, including different types of cancers ( Lin and Beal, 2006 ; Guo et al, 2020 ). Recent studies have indicated that dysfunctional mitochondrial fission is involved in the progression of some malignancies, including glioblastoma, liver cancer and gastric cancer ( Hernandez-Alvarez and Zorzano, 2021 ; Lenzi et al, 2021 ; Zhu et al, 2021 ). Furthermore, some studies have indicated that mitochondrial dynamics have an imperative function in the chemoresistance of cancer cells ( Kong et al, 2015 ; Cai et al, 2016 ; Huang et al, 2018 ).…”

Identified RP2 as a prognostic biomarker for glioma, facilitating glioma pathogenesis mainly via regulating tumor immunity

“…Proteins often need to dock several tertiary structures to each other to form quaternary structures for biological functions and metabolic reactions [ 21 ]. To investigate the potential mechanisms of protein physical interactions, we first selected RP2 to construct a network of proteins with which it can interact ( Supplementary Figure 2A ).…”

Identification and Validation of a m5C RNA Modification-Related Gene Signature for Predicting Prognosis and Immunotherapeutic Efficiency of Gastric Cancer

“…With the development of molecular biology and clinical treatment with precision therapy, researchers have been exploring new prognostic markers of GC at the molecular level. Zhu et al [3] revealed the expression, prognostic value, potential functional networks, protein interactions, and immune infltration of MTFR2 (mitochondrial fssion regulator 2) in GC, concluding that MTFR2 may be a potential prognostic marker and therapeutic target for GC patients. Zhu et al [34] explored the association between VEGFR-2 and the prognosis of GC.…”

“…GC is the ffth most common malignancy worldwide and the third leading cause of global cancer-related mortality [1,2]. Although clinical and surgical conditions improved significantly, the 5-year survival rate for GC patients remains very low, as more than 80% of patients are diagnosed at an advanced stage [3,4]. Now, surgical resection is still the most efective treatment for early GC.…”