PGC-1α Suppresses the Activation of TGF-β/Smad Signaling via Targeting TGFβRI Downregulation by let-7b/c Upregulation

Choi, Hyun-Jun; Kim, Dong-Hyun; Kim, Chang Seong; Bae, Eun Hui; Kwon, Seong; Kim, Soo Wan

doi:10.3390/ijms20205084

Cited by 15 publications

(9 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TGFβ1 is a major inducer of EMT through transcriptional reprogramming with SNAI1, SNAI2, ZEB1, and ZEB2 as well as TWIST1 [ 7 ]. Recent report has shown that PGC1α suppresses TGFβ1/Smad signaling through let-7b/c upregulation [ 52 ]. In addition, suppression of ID1 and ID2 expression by TGFβ1/Smad signaling has been previously observed [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition

Lee

et al. 2021

Cancers

View full text Add to dashboard Cite

PGC1α oppositely regulates cancer metastasis in melanoma, breast, and pancreatic cancer; however, little is known about its impact on lung cancer metastasis. Transcriptome and in vivo xenograft analysis show that a decreased PGC1α correlates with the epithelial–mesenchymal transition (EMT) and lung cancer metastasis. The deletion of a single Pgc1α allele in mice promotes bone metastasis of KrasG12D-driven lung cancer. Mechanistically, PGC1α predominantly activates ID1 expression, which interferes with TCF4-TWIST1 cooperation during EMT. Bioinformatic and clinical studies have shown that PGC1α and ID1 are downregulated in lung cancer, and correlate with a poor survival rate. Our study indicates that TCF4-TWIST1-mediated EMT, which is regulated by the PGC1α-ID1 transcriptional axis, is a potential diagnostic and therapeutic target for metastatic lung cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition

Lee

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…EMT is triggered by many signaling molecules, which interplay with each other to form a crosstalk network. TGF-b signaling, which acts via Smad proteins with intrinsic receptor tyrosine kinase activity, is one of the most important pathways of EMT (Choi et al, 2019). In addition, bone morphogenetic protein, Notch, and Hedgehog activated by various dynamic stimuli from the local microenvironment are also motivators of EMT (Gonzalez and Medici, 2014).…”

Section: Discussionmentioning

confidence: 99%

USP5 Promotes Metastasis in Non-Small Cell Lung Cancer by Inducing Epithelial-Mesenchymal Transition via Wnt/β-Catenin Pathway

Xue

Wang

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Ubiquitin-specific protease 5 (USP5) is a deubiquitinating enzyme that functions as an oncoprotein in a variety of human cancers. However, the expression and role of USP5 in the metastasis of non-small cell lung cancer (NSCLC) have not been addressed. In this study, we examined the expression and prognostic significance of USP5 in NSCLC. The results revealed that USP5 was overexpressed and correlated with metastasis and overall survival in NSCLC tissues. A further in vitro study revealed that the levels of USP5 protein in NSCLC cells were associated with epithelial-mesenchymal transition (EMT) markers. Furthermore, USP5 overexpression significantly enhanced, whereas USP5 silencing significantly decreased the expression of EMT proteins and migration and invasion of NSCLC cells. In addition, the results from western blotting demonstrated that USP5 regulated EMT via the Wnt/b-catenin signaling pathway. Further immunohistochemical analysis revealed that USP5 was significantly associated with the expression of b-catenin and EMT markers in NSCLC tissues. Overall, USP5 upregulation is associated with tumor metastasis and poor prognosis in patients with NSCLC. USP5 promotes EMT and the invasion and migration of NSCLC cells. Therefore, USP5 may serve as a novel prognostic biomarker and provide a potential target for the treatment of metastasis in NSCLC.

show abstract

“…Studies have shown that let-7b is negatively correlated with collagen I and TGFβI [ 24 , 25 , 26 , 27 ], leading us to wonder whether collagen I and TGFβI were target genes of let-7b. We transfected either a let-7b mimic or inhibitor into LX-2 cells.…”

Section: Resultsmentioning

confidence: 99%

The role of let-7b in the inhibition of hepatic stellate cell activation by rSjP40

et al. 2021

View full text Add to dashboard Cite

Background Hepatic stellate cells (HSCs) are one of the main cell types involved in liver fibrosis induced by many factors, including schistosomes. Previous studies in our lab have shown that recombinant P40 protein from Schistosoma japonicum (rSjP40) can inhibit HSC activation in vitro. Let-7b is a member of the let-7 microRNA family and plays an inhibitory role in a variety of diseases and inflammatory conditions. In this study, we investigated the role of let-7b in the inhibition of HSC activation by rSjP40. Methods Expression of let-7b was detected by quantitative real-time PCR. A dual luciferase assay was used to confirm direct interaction between let-7b and collagen I. We also used western blot to assess protein levels of TGFβRI and collagen type I α1 (COL1A1). Results We found that rSjP40 up-regulates expression of let-7b in HSCs. Let-7b inhibits collagen I expression by directly targeting the 3’UTR region of the collagen I gene. Furthermore, we discovered that let-7b inhibitor partially restores the loss of collagen I expression caused by rSjP40. Conclusion Our research clarifies the role of let-7b in the inhibition of HSC activation by rSjP40 and will provide new insights and ideas for the inhibition of HSC activation and treatment of liver fibrosis.

show abstract

PGC-1α Suppresses the Activation of TGF-β/Smad Signaling via Targeting TGFβRI Downregulation by let-7b/c Upregulation

Cited by 15 publications

References 38 publications

PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition

PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition

USP5 Promotes Metastasis in Non-Small Cell Lung Cancer by Inducing Epithelial-Mesenchymal Transition via Wnt/β-Catenin Pathway

The role of let-7b in the inhibition of hepatic stellate cell activation by rSjP40

Contact Info

Product

Resources

About