Expression and prognostic analysis of Rho GTPase-activating protein 11A in lung adenocarcinoma

Chen, Shu-Chen; Duan, He; Xie, Yusai; Li, Xiaoling; Zhao, Yang

doi:10.21037/atm-21-2113

Cited by 7 publications

(6 citation statements)

References 26 publications

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“…Based on previous studies, in addition to NCAPD2, 18 hub genes have also been reported to be overexpressed in lung cancer and contribute to a poor prognosis. [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] Subsequently, we constructed a prognostic model, which exerted a good predictive effect. The above studies further demonstrated that hub genes, including NCAPD2, jointly promote the occurrence and progression of LUAD.…”

Section: Discussionmentioning

confidence: 99%

NCAPD2 is a novel marker for the poor prognosis of lung adenocarcinoma and is associated with immune infiltration and tumor mutational burden

Zheng

et al. 2023

Medicine

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Lung adenocarcinoma (LUAD) is at present the most prevalent subtype of lung cancer worldwide. Non-SMC condensin I complex subunit D2 (NCAPD2) is one of the 3 non-SMC subunits in condensin I. Previous studies have confirmed that NCAPD2 plays a critical role in chromosome cohesion and segregation. NCAPD2 may be involved in tumorigenesis and progression by participating in abnormal cell cycle division, but the prognostic value of NCAPD2 in LUAD remains unclear. We investigated differences in the expression levels of NCAPD2 and determined their association with clinical features, as well as their diagnostic and prognostic value using the cancer genome atlas database. The function of NCAPD2 was analyzed using gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis. CIBERSORT, single-sample gene set enrichment analysis, and ESTIMATE were used to analyze the immune microenvironment of tumor patients. Tumor mutational burden (TMB) and immune checkpoints were analyzed, while hub genes were identified using weighted gene coexpression network analysis and were used to construct prognostic models. Subsequently, the competing endogenous RNAs network of NCAPD2 in LUAD was explored. Finally, we performed qPCR to verify differences in NCAPD2 expression between the tumor and normal tissues. The expression of NCAPD2 in LUAD was significantly upregulated compared with normal lung tissues. NCAPD2 has been linked to the T stage, N stage, and tumor stage. The elevated expression of NCAPD2 in LUAD can predict a poor prognosis. Functional enrichment analysis indicated that the main function of NCAPD2 was in cell cycle regulation. Moreover, NCAPD2 was also associated with immune cell infiltration and TMB. NCAPD2 is a novel prognostic marker in LUAD and is associated with immune infiltration and TMB.Abbreviations: ceRNA = competing endogenous RNA, DEGs = differential expression genes, GO = gene ontology, GSEA = gene set enrichment analysis, KEGG = Kyoto encyclopedia of genes and genomes, LUAD = lung adenocarcinoma, NCAPD2 = Non-SMC condensin I complex subunit D2, PPI = protein-protein interaction, ssGSEA = single-sample gene set enrichment analysis, TCGA = the cancer genome atlas, TMB = tumor mutational burden, WGCNA = weighted gene coexpression network analysis.

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Section: Discussionmentioning

confidence: 99%

NCAPD2 is a novel marker for the poor prognosis of lung adenocarcinoma and is associated with immune infiltration and tumor mutational burden

Zheng

et al. 2023

Medicine

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“…According to a bioinformatic study, ARHGAP6 , 10 , 14 , 19 , 23 , and 24 had the lowest expression, and ARHGAP11 , 15 , 18 , and 30 had overexpression in BC patients compared to normal persons [ 1 ]. Several studies revealed that, in addition to various types of BCs, especially BLBCs, ARHGAP11A has a high expression level in human glioblastoma, colon, lung, hepatocellular, and gastric cancers [ 31 , 74 , 76 ]. Also, it was revealed that applying interfering RNA- (iRNA-) based suppression to ARHGAP11A can decrease the aggressive properties of several cancers which can reveal the oncogenic role of this RhoGAP [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Lawson and Der have indicated in BLBC that cell cycle arrest in the G1 phase occurred by upregulation of p27 (a CDK inhibitor) which is the result of the ARHGAP11A downregulation [ 23 ], and the overexpression of ARHGAP11A in the G1 to S/G2/M phase transition might occur through the p27 reduction and cyclin D1 enhancement. These phenomena can lead to RhoA inhibition and reduce the formation of stress fibers and focal adhesions which leads to stimulating cell migration and invasive features in breast cells, especially BLBCs [ 10 , 23 , 31 , 32 , 74 , 81 ]. Generally, RhoA has a complicated role in various cancer cells; even though some evidence has revealed that RhoA has an oncogenic role in some BC cell lines such as MC7 [ 28 , 82 ], lots of studies have shown that RhoA inhibition can stimulate cell migration and lead to metastasis in BLBCs and TNBC cell lines like MDA-MB-231, which overall indicate the tumor suppressive role of RhoA in most BC cells [ 23 , 28 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

“…GAPs boost the exchange of GTP to GDP to turn GTPase into the inactive form, GEFs promote the catalysis of GDP to GTP that activates GTPase, and GDIs separate GTPases in the GDPbound form to keep the GTPase in an inactive form [28]. ARHGAP11A (Rho GTPase activating protein 11A) encodes a 1023-aa protein with RhoGAP activity located on chromosome 15 (i.e., 15q13.3) [23,[29][30][31]. Recent studies demonstrate that ARHGAP11A has a higher expression in BLBCs than the other subtypes [32].…”

Section: Introductionmentioning

confidence: 99%

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Protooncogenic Role of ARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma: Two Promising Breast Cancer Biomarkers

Naeimzadeh,

Ilbeigi,

Dastsooz

et al. 2023

BioMed Research International

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Invasive duct carcinoma (IDC) is one of the most common types of breast cancer (BC) in women worldwide, with a high risk of malignancy, metastasis, recurrence, and death. So far, molecular patterns among IDC cases have not been fully defined. However, extensive evidence has shown that dysregulated Rho family small GTPases (Rho GTPases) including Rho GTPase activating proteins (RhoGAPs) have important roles in the invasive features of IDCs. In the current study, we analyzed the expression levels of two RhoGAP genes, ARHGAP11A and ARHGAP11B, in The Cancer Genome Atlas (TCGA) breast cancer (BRCA) and also our 51 IDC tumors compared to their matched normal tissues using quantitative polymerase chain reaction (qPCR). Our TCGA data analysis revealed higher expression of ARHGAP11A and ARHGAP11B in various cancers comprising BCs. Also, we found correlations between these genes and other genes in TCGA-BRCA. Moreover, our methylation analysis showed that their promotor methylation had a negative correlation with their overexpression. QPCR revealed their significant upregulation in our tumor samples. Furthermore, we found that the expression level of ARHGAP11A was considerably lower in women who were breastfeeding. Moreover, it had overexpression in cases who had regular menstrual cycles and early age (younger than 14) at menarche. However, ARHGAP11B had a higher expression in HER2-positive tumors versus HER2-positive and ER-positive tumors. Our study found possible protooncogenic roles for these genes and their involvement in IDC pathogenesis and malignancy. Therefore, they can be considered novel prognostic and diagnostic biomarkers for IDC.

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“…The H2afx, also known as H2ax, has been proven to be a marker to distinguish patients with or without liver and lung fibrosis (35) and marrow fibrosis (36). Previous studies attached more attention to the oncogenic role in cancers, including basal-like breast cancer subtype (37) and lung adenocarcinoma (38). The Chek2 plays a key role in cell response to DNA damage, and Chek2 loss has been confirmed to improve partially skeletal growth in parathyroid hormonerelated peptide 1-84 knockin mice (39).…”

Section: Discussionmentioning

confidence: 99%

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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Expression and prognostic analysis of Rho GTPase-activating protein 11A in lung adenocarcinoma

Cited by 7 publications

References 26 publications

NCAPD2 is a novel marker for the poor prognosis of lung adenocarcinoma and is associated with immune infiltration and tumor mutational burden

NCAPD2 is a novel marker for the poor prognosis of lung adenocarcinoma and is associated with immune infiltration and tumor mutational burden

Protooncogenic Role of ARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma: Two Promising Breast Cancer Biomarkers

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

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