RGS6 suppresses TGF-β-induced epithelial–mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4

Wang, Zhao; Wang, Shengjie; Sun, Zelong; Li, Zhe; Zhang, Hong Tao; Huang, Jie

doi:10.1038/s41419-022-05093-0

Cited by 20 publications

(10 citation statements)

References 63 publications

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“…Studies have shown that FOXN3 suppresses the mRNA and protein expression of E2F5 by inhibiting the promoter activity of potential oncogene E2F5 , thereby inhibiting the proliferation of HCC cells in vitro and in vivo ( 43 ). Another tumor suppressor, regulator of G protein signaling 6 ( RGS6 ), is upregulated in the liver of NAFLD patients, forms a complex with ATM in the liver, promotes ATM phosphorylation, and drives hepatic steatosis ( 44 , 45 ). A study confirmed that hepatic RGS6 increases oxidative stress and inflammation, which drive lipid deposition, fibrosis, and nonalcoholic fatty liver disease ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of shared genetic architecture between non-alcoholic fatty liver disease and type 2 diabetes: A genome-wide analysis

Tan

Chan

2023

Front. Endocrinol.

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BackgroundThe incidence of complications of non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) has been increasing.MethodIn order to identify the shared genetic architecture of the two disease phenotypes of NAFLD and T2D, a European population-based GWAS summary and a cross-trait meta-analysis was used to identify significant shared genes for NAFLD and T2D. The enrichment of shared genes was then determined through the use of functional enrichment analysis to investigate the relationship between genes and phenotypes. Additionally, differential gene expression analysis was performed, significant differentially expressed genes in NAFLD and T2D were identified, genes that overlapped between those that were differentially expressed and cross-trait results were reported, and enrichment analysis was performed on the core genes that had been obtained in this way. Finally, the application of a bidirectional Mendelian randomization (MR) approach determined the causal link between NAFLD and T2D.ResultA total of 115 genes were discovered to be shared between NAFLD and T2D in the GWAS analysis. The enrichment analysis of these genes showed that some were involved in the processes such as the decomposition and metabolism of lipids, phospholipids, and glycerophospholipids. Additionally, through the use of differential gene expression analysis, 15 core genes were confirmed to be linked to both T2D and NAFLD. They were correlated with carcinoma cells and inflammation. Furthermore, the bidirectional MR identified a positive causal relationship between NAFLD and T2D.ConclusionOur study determined the genetic structure shared between NAFLD and T2D, offering a new reference for the genetic pathogenesis and mechanism of NAFLD and T2D comorbidities.

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Section: Discussionmentioning

confidence: 99%

Identification of shared genetic architecture between non-alcoholic fatty liver disease and type 2 diabetes: A genome-wide analysis

Tan

Chan

2023

Front. Endocrinol.

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“…In addition to regulation by non-coding RNAs, TGF-β can exert its influence on EMT by other effectors; G-protein regulator signaling 6, a tumor suppressor protein that negatively regulates TGF-β-induced EMT in NSCLC, and its low expression was associated with poor survival, which suggests that it is a possible LC prognostic marker [ 37 ]. In addition to QKI-5, an important protein involved in the RNA signal transduction, it has been shown that this protein decreased in metastatic lung adenocarcinoma, and its overexpression inhibits TGF-β-induced EMT-mediated invasion and metastasis via TGFβRI [ 38 ].…”

Section: Tgf-β Molecular Mechanism In Lung Cancermentioning

confidence: 99%

TGF-β as Predictive Marker and Pharmacological Target in Lung Cancer Approach

Ramundo

Palazzo

Aldieri

2023

Cancers

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Lung cancer (LC) represents the leading cause of cancer incidence and mortality worldwide. LC onset is strongly related to genetic mutations and environmental interactions, such as tobacco smoking, or pathological conditions, such as chronic inflammation. Despite advancement in knowledge of the molecular mechanisms involved in LC, this tumor is still characterized by an unfavorable prognosis, and the current therapeutic options are unsatisfactory. TGF-β is a cytokine that regulates different biological processes, particularly at the pulmonary level, and its alteration has been demonstrated to be associated with LC progression. Moreover, TGF-β is involved in promoting invasiveness and metastasis, via epithelial to mesenchymal transition (EMT) induction, where TGF-β is the major driver. Thus, a TGF-β-EMT signature may be considered a potential predictive marker in LC prognosis, and TGF-β-EMT inhibition has been demonstrated to prevent metastasis in various animal models. Concerning a LC therapeutic approach, some TGF-β and TGF-β-EMT inhibitors could be used in combination with chemo- and immunotherapy without major side effects, thereby improving cancer therapy. Overall, targeting TGF-β may be a valid possibility to fight LC, both in improving LC prognosis and cancer therapy, via a novel approach that could open up new effective strategies against this aggressive cancer.

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“…The canonical function of RGS proteins is to act as GTPase-activating proteins (GAPs), accelerate GTP hydrolysis on G-protein alpha subunits, and terminate signaling pathways downstream of G protein-coupled receptors (Hunt et al, 1996). RGS proteins can have noncanonical GAP-independent functions, including the suppression of transforming growth factor beta (TGF-β)-induced EMT in non-small cell lung cancer by RGS6 (Wang et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer

Liu,

Jiang,

Qiu

et al. 2024

Preprint

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Distant metastasis is the major cause of death in patients with breast cancer. Epithelial–mesenchymal transition (EMT) contributes to breast cancer metastasis. Regulator of G protein-signaling (RGS) proteins modulate metastasis in various cancers. This study identified a novel role for RGS10 in EMT and metastasis in breast cancer. RGS10 protein levels were significantly lower in breast cancer tissues compared to normal breast tissues, and deficiency in RGS10 protein predicted a worse prognosis in patients with breast cancer. RGS10 protein levels were lower in the highly aggressive cell line MDA-MB-231 than in the poorly aggressive, less invasive cell lines MCF7 and SKBR3. Silencing RGS10 in SKBR3 cells enhanced EMT and caused SKBR3 cell migration and invasion. The ability of RGS10 to suppress EMT and metastasis in breast cancer was dependent on lipocalin-2 and miR-539-5p. These findings identify RGS10 as a tumor suppressor, prognostic biomarker, and potential therapeutic target for breast cancer.

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RGS6 suppresses TGF-β-induced epithelial–mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4

Cited by 20 publications

References 63 publications

Identification of shared genetic architecture between non-alcoholic fatty liver disease and type 2 diabetes: A genome-wide analysis

Identification of shared genetic architecture between non-alcoholic fatty liver disease and type 2 diabetes: A genome-wide analysis

TGF-β as Predictive Marker and Pharmacological Target in Lung Cancer Approach

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer

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