Role of Rab GTPases in Hepatocellular Carcinoma

Yang, Chuncheng; Meng, Guang-Xiao; Dong, Zhao‐Ru; Li, Tao

doi:10.2147/jhc.s336251

Cited by 5 publications

(7 citation statements)

References 72 publications

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“…Overexpression of RAB42 is correlated with the contents of immune infiltration, types of immune-infiltrating cells, and expression of immune checkpoints. These results mirror well with the results from other studies ( Yang C. C. et al, 2021 ; Peng et al, 2022 ; Kong et al, 2023 ). Previous study shown that RAB42 is positively correlated with exhausted CD8 + T cells in liver cancer ( Peng et al, 2022 ).…”

Section: Discussionsupporting

confidence: 92%

“…Dysregulated expression of RAB proteins is tightly associated with malignances ( Tzeng and Wang, 2016 ; Jin et al, 2021 ). Furthermore, overexpression of certain RAB GTPase can augment the proliferation, invasion and migration of some cancer cell types ( Yang C. C. et al, 2021 ). For example, RAB9A overexpression promotes the proliferation and invasion of liver hepatocellular carcinoma (LIHC) cells ( Sun et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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RAB42 overexpression correlates with poor prognosis, immune cell infiltration and chemoresistance

Wang,

Xie,

Qian

et al. 2024

Front. Pharmacol.

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BackgroundRAB42 (Ras-related protein 42) is a new small GTPase that controls the vesicular trafficking from endosomes to trans-Golgi network in mammalian cells. However, the role of RAB42 in multiple cancers, especially in liver hepatocellular carcinoma (LIHC), has not been well investigated.MethodsA variety of cancer-related databases and online tools, including TCGA, GTEx, TARGET, QUANTISEQ, EPIC, RNAactDrug, CTR-DB, TIMER algorithms and Sangerbox, were applied to explore the correlation of RAB42 expression with prognosis, immune microenvironment, immune regulatory network, RNA modification, pathway activation and drug sensitivity in pan-cancer. The prognostic, immunomodulatory and tumor-promoting effects of RAB42 were verified in various malignancies and determined by a series of in vitro cellular experiments.ResultsRAB42 is significantly overexpressed in most cancers with advanced pathological stages. Its overexpression is correlated with poor survival in pan-cancer. RAB42 overexpression has a high diagnostic accuracy of various cancers (AUC > 0.80). RAB42 overexpression not only correlates with distinct stromal immune infiltration and level of immune checkpoint molecules, but also associates with weak immune cell infiltration, immunomodulatory genes expression, and immunotherapeutic response to immune checkpoint inhibitors (ICIs). Additionally, RAB42 overexpression correlates with enhanced expression of m6A RNA methylation-related genes (MRGs) and its interactors. Moreover, overexpression of RAB42 serves as a drug-resistant marker to certain chemotherapies and acts as a potential biomarker for LIHC. Notably, RAB42 overexpression or activation promotes the cellular proliferation, migration and invasion of LIHC.ConclusionOverexpressed RAB42 serves as a potential prognostic biomarker and therapeutic target in pan-cancer, especially in LIHC.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

RAB42 overexpression correlates with poor prognosis, immune cell infiltration and chemoresistance

Wang,

Xie,

Qian

et al. 2024

Front. Pharmacol.

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“…Each Rab GTPases localizes in a specific subcellular structure and exerts its respective membrane trafficking functions (Stenmark, 2009). Previous studies have reported that several Rab GTPases are involved in HCC progression, including modulating proliferation, migration, invasion, and metastasis (Yang et al, 2021). RAB6B, an isoform of RAB6, is mainly located in the Golgi apparatus and plays a role in Golgi-to-ER retrograde transport (Wanschers et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…The Rab GTPase is a family of proteins that mediate membrane trafficking, and distinct Rab proteins located in specific organelles are involved in the regulation of cell growth, survival, and death (Gopal Krishnan et al, 2020). Additionally, accumulating studies have reported that dysregulated expression or mutation of several Rab proteins may affect tumor migration, invasion, metastasis, stromal cell communication, and drug resistance in HCC (Yang et al, 2021). RAB6B is an isoform protein of the RAB6 subfamily, mainly located in the Golgi complex (Opdam et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma

Peng

Zhu²,

Wang³

et al. 2022

Front. Pharmacol.

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Backgrounds: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the second leading cause of death among all cancers. The Ras-associated binding (Rab) proteins constitute the largest family of the Ras superfamily of small GTPases, which mainly mediate membrane trafficking processes. RAB6B is a member of Rab GTPases, and it has been found to be dysregulated in various tumors. However, the clinical significance, correlations with immune cells, and stroma infiltration of RAB6B in HCC remain unclear.Methods: RAB6B mRNA and protein expression in HCC were examined using the TIMER, HCCDB, UALCAN, and HPA databases. The genetic alterations of RAB6B were analyzed by cBioPortal and COSMIC databases. The correlations between RAB6B and tumor-infiltrating immune cells and cancer-associated fibroblasts were explored by using TIMER, TISIDB, and GEPIA databases. Co-expression networks of RAB6B were investigated based on LinkedOmics. Drug sensitivity was analyzed through the GDSC and CTRP databases. RAB6B was knocked down with siRNA in HCC cell lines. EdU assay was performed to detect the cell proliferation ability, flow cytometry was used to compare the differences in the ability of apoptosis, and MTT was used to evaluate the drug sensitivity in vitro.Results: RAB6B mRNA and protein expression were upregulated in the HCC tissues. Kaplan–Meier and Cox regression analyses suggested that highly expressed RAB6B was an independent prognostic factor for poor survival in HCC patients. Moreover, we found that RAB6B expression was positively correlated with the infiltration of immune cells in HCC, including some immunosuppressive cells, chemokines, and receptors, meanwhile RAB6B expression was associated with CD8+T cells exhaustion, resulting in an immunosuppressive microenvironment. Additionally, functional enrichment analysis indicated that RAB6B may be involved in ECM remodeling in the TME, and RAB6B expression was positively associated with CAFs infiltration. Furthermore, RAB6B presented a positive association with sensitivity to GDSC and CTRP drugs. RAB6B knockdown inhibited the cell proliferation and promoted apoptosis and sensitivity to cisplatin of HCC cells in vitro.Conclusion: Our study revealed that RAB6B is a potential biomarker for poor prognosis in HCC patients and correlates with the formation of the immunosuppressive microenvironment in HCC.

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“…Their activity is regulated by guanine exchange factors (GEF) and GTPase activating factors (126). In HCC, RABs promote replication of HBV and HCV, and their involvement of membrane trafficking can stimulate cell proliferation, invasion, metastasis, and drug resistance (127).…”

Section: Circular Rnas Activating Ras-related Small Gtpases (Rabs)mentioning

confidence: 99%

Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in PreclinicalIn VivoModels

WEIDLE,

NOPORA

2023

Cancer Genomics Proteomics

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Role of Rab GTPases in Hepatocellular Carcinoma

Cited by 5 publications

References 72 publications

RAB42 overexpression correlates with poor prognosis, immune cell infiltration and chemoresistance

RAB42 overexpression correlates with poor prognosis, immune cell infiltration and chemoresistance

RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma

Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in PreclinicalIn VivoModels

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