ARHGAP11A Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric Cancer

Fan, Biao; Ji, Ke; Bu, Zhaode; Zhang, Ji; Yang, Huadong; Li, Jialin; Wu, Xiaojiang

doi:10.3389/fmolb.2021.720645

Cited by 12 publications

(8 citation statements)

References 44 publications

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“…ARHGAP11A, a prognostic biomarker, is correlated with immune infiltrates in gastric cancer. In addition, high ARHGAP11A expression significantly correlated with a better prognosis in gastric cancer (41). However, the role of ARHGAP11A in glioma remains unclear.…”

Section: Discussionmentioning

confidence: 99%

TRAF3IP3 promotes glioma progression through the ERK signaling pathway

Chen²,

Zhang³

et al. 2022

Front. Oncol.

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TRAF3IP3 was reportedly associated with poor prognosis in patients with melanoma; however, its role in glioma is unknown. We aimed to demonstrate the relationship between TRAF3IP3 and glioma and to investigate the potential role of TRAF3IP3 in glioma. Datasets were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We used the Wilcoxon rank-sum test to compared TRAF3IP3 expression in normal and glioma tissues. Kaplan-Meier analysis was performed to evaluate the correlation between TRAF3IP3 and patient survival rate. Gene set enrichment analysis (GSEA) was used to annotate the biological function of TRAF3IP3 in glioma. We also examined the effects of TRAF3IP3 on glioma progression, including characteristics such as cell proliferation, migration, and invasion, using cell proliferation, wound healing, and Transwell assays, respectively, paired with in vitro glioma cell lines and in vivo mouse xenograft models to determine the molecular mechanisms underlying these effects. High TRAF3IP3 expression in glioma tissues was associated with patients with neoplasm cancer tissue source site, and poorer overall survival (OS) (p = 0.03), which was validated using TCGA. GSEA revealed the enrichment of neuroactive ligand-receptor interactions, the olfactory pathway, proteasome pathway, cytokine-cytokine receptor interactions, and calcium signaling pathway in the TRAF3IP3 high-expression phenotype. TRAF3IP3 knockdown markedly suppressed the proliferation, migration, and invasion abilities of U251 glioma cells, whereas TRAF3IP3 overexpression notably promoted the progression of U118 cell tumors. Mechanistic studies revealed that TRAF3IP3 upregulated p-ERK expression in glioma cells. Notably, the ERK signaling pathway inhibitor U0126 drastically attenuated the effects of TRAF3IP3 on p-ERK and markedly blocked its tumorpromoting activity. TRAF3IP3 overexpression also promoted in vivo tumor growth in a nude mouse xenograft model. Collectively, TRAF3IP3 stimulates glioma cell proliferation, migration, and invasion, at least partly by activating the ERK signaling pathway. We hypothesize that TRAF3IP3 may participate in glioma development via the ERK signaling pathway and that elevated TRAF3IP3 expression may serve as a potential biomarker for glioma prognosis.

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Section: Discussionmentioning

confidence: 99%

TRAF3IP3 promotes glioma progression through the ERK signaling pathway

Chen²,

Zhang³

et al. 2022

Front. Oncol.

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“…The Arhgap11a is a protein-coding gene that locates on chr15q13.3, encoding a member of GTPaseactivating proteins (RhoGAPs), which are upstream regulators of Rho GTPases. The Rho GTPases are a subfamily of the Ras superfamily proteins, which play central roles in multiple biological processes, such as cell motility, cell polarity, cell cycle progression, cell adhesion, migration, and invasion (47). Our study firstly demonstrated targeted inhibition of Arhgap11a by miR-211-facilitated osteogenic differentiation of MC3T3-E1 cells.…”

Section: Discussionmentioning

confidence: 69%

Involvement of MiRNA-211-5p and Arhgap11a Interaction During Osteogenic Differentiation of MC3T3-E1 Cells

Zhang

et al. 2022

Front. Surg.

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ObjectiveMicroRNAs (miRNAs) are well-recognized for their abilities to regulate gene expression post-transcriptionally in plants and animals. Recently, miRNA-messenger RNA (mRNA) regulatory relationships have been confirmed during biological processes, including osteogenic differentiation. This study aimed to find out more candidate miRNA-mRNA pairs involved in the osteogenic differentiation of MC3T3-E1 cells.MethodsAn MC3T3-E1-based microarray dataset (accessioned as GSE46400) downloaded from the Gene Expression Omnibus included MC3T3-E1 cells with or without 14-day osteoblast differentiation osteoblast induction. Multiple miRNA-mRNA prediction databases were searched by differentially expressed genes (DEGs) to obtain pairs of a miRNA-DEG regulatory network. The MC3T3-E1 cells were cultured and incubated in the osteogenic differentiation medium for 14 days. The expressions of candidate miRNAs and mRNAs were determined by real-time quantitative PCR(RT-qPCR) in MC3T3-E1 cells. The miRNA-mRNA interactions were verified by dual-luciferase reporter gene assays and experiments using mimics miRNA or their inhibitors.ResultsWe identified 715 upregulated DEGs and 603 downregulated DEGs between MC3T3-E1 cells with and without osteoblast induction by analyzing the raw data of the GSE46400 dataset. There were 7 overlapped miRNA-mRNA pairs identified during osteogenic differentiation of MC3T3-E1 cells, including mmu-miR-204-5p-Arhgap11a, mmu-miR-211-5p-Arhgap11a, mmu-miR-24-3p-H2afx, mmu-miR-3470b-Chek2, mmu-miR-3470b-Dlgap5, mmu-miR-466b-3p-Chek1, and mmu-miR-466c-3p-Chek1. The Arhgap11a, H2afx, Chek2, Dlgap5, and Chek1 were hub genes downregulated in MC3T3-E1 cells after osteogenic differentiation, verified by RT-qPCR results. The RT-qPCR also determined declined expressions of miR-204-5p and miR-24-3p concomitant with elevated expressions of miR-211-5p, miR-3470b, miR-466b-3p, and miR-466c-3p in the MC3T3-E1 cells, with osteoblast induction compared with undifferentiated MC3T3-E1 cells. Dual-luciferase reporter gene assays demonstrated Arhgap11a as the target of miR-211-5p. MiR-211-5p upregulation by its mimic increased Arhgap11a expression in MC3T3-E1 cells.ConclusionOur study characterizes miR-211-5p targeting Arhgap11a promotes the osteogenic differentiation of MC3T3-E1 cells, which provides novel targets to promote the osteogenesis process during bone repair.

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“…Journal Pre-proof kinase 2 beta (CSNK2B) and HRAS proto-oncogene, GTPase (HRAS) (Supplementary Figure 2 and supplementary Table 2). ARHGAP11A is reported to be overexpressed in a variety of tumours and to play an important role in the proliferation, invasion, metastasis, and cell cycle regulation of tumour cells [24]. SMEK1 overexpression was associated with a 2.8-fold decrease CSNK2B, the regulatory subunit of the serine/threonine protein kinase Casein kinase 2 whose activity is associated with apoptosis suppression [25,26].…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%