Ral signaling pathway in health and cancer

Moghadam, Adel Rezaei; Patrad, Elham; Tafsiri, Elham; Peng, Warner; Fangman, Benjamin D; Pluard, Timothy; Accurso, Anthony; Salacz, Michael; Shah, Kushal; Ricke, Brandon; Bi, Danse; Kimura, Kyle; Graves, Leland; Najad, Marzieh Khajoie; Dolatkhah, Roya; Sanaat, Zohreh; Yazdi, Mina; Tavakolinia, Naeimeh; Mazani, Mohammad; Amani, Mojtaba; Ghavami, Saeid; Gartell, Robyn; Reilly, Colleen; Zaid, Naima,; Esfandyari, Tuba; Farassati, Faris

doi:10.1002/cam4.1105

Cited by 42 publications

(29 citation statements)

References 166 publications

(254 reference statements)

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“…Besides, RALGPS2, Ral guanine nucleotide exchange factor with PH domain and SH3 domain-binding motif 2, is a Ras-independent guanine nucleotide exchange factor (GEF) for Ras-related protein Ral-A (RalA) GTPase containing a PH domain and an SH3-binding region, and it is involved in cytokinesis, cell cycle, and cytoskeleton rearrangement [ 36 ]. Although RalA and RalGEFs are implicated in tumorigenesis, there are few data for RalGPS2 role in lung cancer [ 37 ]. Santos et al showed that RALGPS2 is involved in the control of cell cycle progression in NSCLC cell lines but did not include its association with clinical features [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis of Three Novel Competing Endogenous RNA Biomarkers with a Prognostic Value in Lung Adenocarcinoma

Tan

Wang

Song

et al. 2020

BioMed Research International

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Increasing evidence has shown competitive endogenous RNAs (ceRNAs) play key roles in numerous cancers. Nevertheless, the ceRNA network that can predict the prognosis of lung adenocarcinoma (LUAD) is still lacking. The aim of the present study was to identify the prognostic value of key ceRNAs in lung tumorigenesis. Differentially expressed (DE) RNAs were identified between LUAD and adjacent normal samples by limma package in R using The Cancer Genome Atlas database (TCGA). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway function enrichment analysis was performed using the clusterProfiler package in R. Subsequently, the LUAD ceRNA network was established in three steps based on ceRNA hypothesis. Hub RNAs were identified using degree analysis methods based on Cytoscape plugin cytoHubba. Multivariate Cox regression analysis was implemented to calculate the risk score using the candidate ceRNAs and overall survival information. The survival differences between the high-risk and low-risk ceRNA groups were determined by the Kaplan-Meier and log-rank test using survival and survminer package in R. A total of 2,989 mRNAs, 185 lncRNAs, and 153 miRNAs were identified. GO and KEGG pathway function enrichment analysis showed that DE mRNAs were mainly associated with “sister chromatid segregation,” “regulation of angiogenesis,” “cell adhesion molecules (CAMs),” “cell cycle,” and “ECM-receptor interaction.” LUAD-related ceRNA network was constructed, which comprised of 54 nodes and 78 edges. Top ten hub RNAs (hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-340-5p, hsa-miR-377-3p, hsa-miR-21-5p, hsa-miR-326, SNHG1, RALGPS2, and PITX2) were identified according to their degree. Kaplan-Meier survival analyses demonstrated that hsa-miR-21-5p and RALGPS2 had a significant prognostic value. Finally, we found that a high risk of three novel ceRNA interactions (SNHG1-hsa-miR-21-5p-RALGPS2, SNHG1-hsa-miR-326-RALGPS2, and SNHG1-hsa-miR-377-3p-RALGPS2) was positively associated with worse prognosis. Three novel ceRNAs (SNHG1-hsa-miR-21-5p-RALGPS2, SNHG1-hsa-miR-326-RALGPS2, and SNHG1-hsa-miR-377-3p-RALGPS2) might be potential biomarkers for the prognosis and treatment of LUAD.

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Section: Discussionmentioning

confidence: 99%

Integrative Analysis of Three Novel Competing Endogenous RNA Biomarkers with a Prognostic Value in Lung Adenocarcinoma

Tan

Wang

Song

et al. 2020

BioMed Research International

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“…Elk-1 is a transcription factor that directs gene expression of c-Myc and its co-transcription factor, Myc-associated zinc-finger (MAZ) [97,98]. MAZ upregulates Ras expression and then activates NF-κB through the RalGEF/Ral/NF-κB cascade and finally activates the EMT [97,99]. In addition, NF-κB is involved in the heterotrimer G-protein signaling network, which mediates cell adhesion signals through guanine nucleotide-binding protein subunit α-15 (GNA15), and Rho, which promotes CXCL5 expression [100,101].…”

Section: Ras Signalingmentioning

confidence: 99%

Ras and Wnt Interaction Contribute in Prostate Cancer Bone Metastasis

2020

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Prostate cancer (PCa) is one of the most prevalent and malignant cancer types in men, which causes more than three-hundred thousand cancer death each year. At late stage of PCa progression, bone marrow is the most often metastatic site that constitutes almost 70% of metastatic cases of the PCa population. However, the characteristic for the osteo-philic property of PCa is still puzzling. Recent studies reported that the Wnt and Ras signaling pathways are pivotal in bone metastasis and that take parts in different cytological changes, but their crosstalk is not well studied. In this review, we focused on interactions between the Wnt and Ras signaling pathways during each stage of bone metastasis and present the fate of those interactions. This review contributes insights that can guide other researchers by unveiling more details with regard to bone metastasis and might also help in finding potential therapeutic regimens for preventing PCa bone metastasis.

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“…Moreover, Moghadam et al observed more intensive oncogenic activity of the Ras-related protein Ral-A (RalA) in CD24+ cancer cells in comparison to CD24− cancer cells. Overexpression and increased RalA activity is predominant in PC and it is associated with tumorigenic growth [27] [28]. CD24 also seems to be involved in integrin-associated cell to matrix adhesion and regulation of cellular morphology through stress fibers, processes of rounding, and nuclear condensation, and therefore protects cancer cells from apoptosis [25].…”

Section: Cd24mentioning

confidence: 99%

Markers of pancreatic cancer stem cells and their clinical and therapeutic implications

et al. 2019

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Pancreatic cancer (PC) is the fourth most common cause of death among all cancers. Poor prognosis of PC may be caused by a prevalence of cancer stem cells (CSCs). CSCs are a population of cancer cells showing stem cell-like characteristics. CSCs have the ability to self-renew and may initiate tumorigenesis. PC CSCs express markers such as CD133, CD24, CD44, DCLK1, CXCR4, ESA, Oct4 and ABCB1. There is a wide complexity of interaction and relationships between CSC markers in PC. These markers are negative prognostic factors and are connected with tumor recurrence and clinical progression. Additionally, PC CSCs are resistant to treatment with gemcitabine. Thus, most current therapies for PC are ineffective. Numerous studies have shown, that targeting of these proteins may increase both disease-free and overall survival in PC.

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Ral signaling pathway in health and cancer

Cited by 42 publications

References 166 publications

Integrative Analysis of Three Novel Competing Endogenous RNA Biomarkers with a Prognostic Value in Lung Adenocarcinoma

Integrative Analysis of Three Novel Competing Endogenous RNA Biomarkers with a Prognostic Value in Lung Adenocarcinoma

Ras and Wnt Interaction Contribute in Prostate Cancer Bone Metastasis

Markers of pancreatic cancer stem cells and their clinical and therapeutic implications

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