Gimap5 Inhibits Lung Cancer Growth by Interacting With M6PR

Dai, Pei; Tang, Zhongxiang; Ruan, Pinglang; Bajinka, Ousman; Liu, Dan; Tan, Yurong

doi:10.3389/fonc.2021.699847

Cited by 10 publications

(17 citation statements)

References 38 publications

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“…The GIMAP genes encode GTP‐binding proteins, which have a unique primary structure and whose function is largely unknown. Our previous studies confirmed that Gimap5 can interact with M6PR and promote the translocation of M6PR to the cell membrane 21 . Our study showed that bronchial epithelial cells predominantly express M6PR‐CI, suggesting the importance of this receptor in epithelial cells.…”

Section: Discussionsupporting

confidence: 83%

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Gimap5 promoted RSV degradation through interaction with M6PR

Dai

Ruan

Mao

et al. 2022

Journal of Medical Virology

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Respiratory syncytial virus (RSV) is one of the main pathogens of viral pneumonia and bronchiolitis in infants and young children and life‐threatening diseases among infants and young children. GTPases of the immune‐associated protein family (GIMAP) are new family members of immune‐associated GTPases. In recent years, much attention has been paid to the function of the GIMAP family in coping with infection and stress. Gimap5 is a member of the GIMAP family, which may be correlated with anti‐infectious immunity. RT‐qPCR, Western blot, and indirect immunofluorescence (IFA) were used to detect the expression of Gimap5, M6PR and IGF1R(the major RSV receptor). Transmission electron microscopy (TEM) was used to detect the degradation of RSV in Gimap5‐overexpressed or ‐silent cell lines. Computer virtual screening was used to screen small molecule compounds targeting Gimap5 and the anti‐RSV effects were explored through in vivo and in vitro experiments. GIMAP5 and M6PR were significantly downregulated after RSV infection. Gimap5 accelerated RSV degradation in lysosomes by interacting with M6PR, and further prevented RSV invasion by downregulating the expression of RSV surface receptor IGF1R. Three small molecule compounds targeting Gimap5 were confirmed to be the agonists of Gimap5. The three compounds effectively inhibited RSV infection and RSV‐induced complications. Gimap5 promotes the degradation of RSV and its receptor through interacting with M6PR. Gimap5 agonists can effectively reduce RSV infection and RSV‐induced complication in vivo and in vitro, which provides a new choice for the treatment of RSV.

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Section: Discussionsupporting

confidence: 83%

“…20 We also found in a previous study that Gimap5 directly interacted with M6PR and promoted its translocation to cell membrane. 21 Therefore, we sought to explore the function of Gimap5 in response to RSV infection. Does the interaction between Gimap5 and M6PR inhibit RSV infection?…”

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confidence: 99%

Gimap5 promoted RSV degradation through interaction with M6PR

Dai

Ruan

Mao

et al. 2022

Journal of Medical Virology

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“…Similarly, we detected the increase in proteins related to the immune system with anti-tumorigenic effects, such as GTPase IMAP family member 5 (GIMA5), described as a promoter of CD4+ T-cell survival and homeostasis [ 57 , 58 ]. GIMA5 also suppresses the proliferation of lung cancer cell lines [ 59 ]. In addition, we observed the increment of proteins such as mitogen-activated protein kinase 2 (MAP4K2), usually expressed in B cells of the germinal center and macrophages, which activates the c-Jun N-terminal kinases [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

Deep Proteomic Analysis on Biobanked Paraffine-Archived Melanoma with Prognostic/Predictive Biomarker Read-Out

Szadai

Velásquez

Szeitz

et al. 2021

Cancers

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The discovery of novel protein biomarkers in melanoma is crucial. Our introduction of formalin-fixed paraffin-embedded (FFPE) tumor protocol provides new opportunities to understand the progression of melanoma and open the possibility to screen thousands of FFPE samples deposited in tumor biobanks and available at hospital pathology departments. In our retrospective biobank pilot study, 90 FFPE samples from 77 patients were processed. Protein quantitation was performed by high-resolution mass spectrometry and validated by histopathologic analysis. The global protein expression formed six sample clusters. Proteins such as TRAF6 and ARMC10 were upregulated in clusters with enrichment for shorter survival, and proteins such as AIFI1 were upregulated in clusters with enrichment for longer survival. The cohort’s heterogeneity was addressed by comparing primary and metastasis samples, as well comparing clinical stages. Within immunotherapy and targeted therapy subgroups, the upregulation of the VEGFA-VEGFR2 pathway, RNA splicing, increased activity of immune cells, extracellular matrix, and metabolic pathways were positively associated with patient outcome. To summarize, we were able to (i) link global protein expression profiles to survival, and they proved to be an independent prognostic indicator, as well as (ii) identify proteins that are potential predictors of a patient’s response to immunotherapy and targeted therapy, suggesting new opportunities for precision medicine developments.

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“…TMEM176B represses adenosine triphosphate (ATP) and nigericin-induced NLRP3 in ammasome activation in dendritic cells and macrophages through ionic mechanisms. Targeting TMEM176B can emphasise anti-tumoral CD8 + T cell responses in an in ammasome-dependent manner while directly killing malignant cells 43,44 .…”

Section: Discussionmentioning

confidence: 99%

Comparative genome-wide analysis of hub lncRNAs and mRNAs in brain metastatic small cell lung cancer – An in-Silico Approach

Namini

Jahangir

Mohseni

et al. 2022

Preprint

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Lung cancer is one of the most commonly prevalent globally. Metastatic lung tumours lead to most deaths in lung cancer. Predicting and preventing tumour metastasis is crucially Important for patient survivability. Hence, in the current study, we focused on a comprehensive analysis of lung cancer patients' differentially expressed genes (DEGs) on brain metastasis cell lines. DEGs are analysed through KEGG and GO databases for the most critical biological processes and pathways for enriched DEGs. Additionally, we performed PPI, GeneMANIA and Kaplan-Meier survival analyses on our DEGs. This article focused on mRNA and lncRNA DEGs for LC patients with brain metastasis and underlying molecular mechanisms. The expression data was gathered from the Gene Expression Omnibus database (GSE161968). We demonstrate that 30 distinct genes are up expressed in brain metastasis SCLC patients, and 31 genes are down-expressed. All the analyses we performed show these genes are Involve In metastatic SCLC. PPI analysis revealed two hub genes (CAT and APP). The results of this article present three lncRNAs, Including XLOC_l2_000941, LOC100507481, and XLOC_l2_007062, also notable mRNAs, have a close relation with brain metastasis in lung cancer and may have a role in the epithelial-mesenchymal transition (EMT) in tumour cells.

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Gimap5 Inhibits Lung Cancer Growth by Interacting With M6PR

Cited by 10 publications

References 38 publications

Gimap5 promoted RSV degradation through interaction with M6PR

Gimap5 promoted RSV degradation through interaction with M6PR

Deep Proteomic Analysis on Biobanked Paraffine-Archived Melanoma with Prognostic/Predictive Biomarker Read-Out

Comparative genome-wide analysis of hub lncRNAs and mRNAs in brain metastatic small cell lung cancer – An in-Silico Approach

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