PGC1α Cooperates with FOXA1 to Regulate Epithelial Mesenchymal Transition through the TCF4-TWIST1

Fang, Xue-Quan; Lee, Mingyu; Lim, Woo-Jin; Lee, Seonghoon; Lim, Chang-Hoon; Lim, Ji-Hong

doi:10.3390/ijms23158247

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…In some cell types, TCF4 gradually becomes an important regulator of epithelial-mesenchymal transformation (EMT) and plays an important role in embryonic development, tissue repair and cancer metastasis. Various convergent lines of evidence support the role of TCF4 as an EMT regulator in different cells ( 26 ). Liu et al demonstrated that TCF4 might play a tumorigenic role in epithelial ovarian cancer and is a useful independent prognostic indicator ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

In vitro study of miRNA-369-3p targeting TCF4 regulating the malignant biological behavior of colon cancer cells

Li,

Sun,

Granados-López

et al. 2023

J Gastrointest Oncol

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Background Colorectal carcinoma (CRC) is a common malignant tumor of the digestive tract. It is characterized by a high degree of malignancy, early metastasis and poor prognosis. Studies have shown the effect of miR-369-3p on the biological function of a variety of tumors. However, the mechanism by which miR-369-3p and its potential target genes participate in the pathogenesis of CRC has not been elucidated. This study aims to study the relationship between miR-369-3p and transcription factor 4 (TCF4), to reveal the mechanism of the occurrence and development of CRC, and to provide a promising target for the treatment of CRC. Methods Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the miR-369-3p levels in CRC tissues and cells. miR-369-3p mimics and/or TCF4 overexpression vectors were transfected into SW480 cells. The expression of miR-369-3p and TCF4 mRNA was detected using RT-qPCR. Bioinformatics analysis predicted the binding site of miR-369-3p to the TCF4 3'UTR, and the targeting relationship was verified by a dual luciferase reporter gene assay. Cell proliferation and invasion were investigated by labeled immunofluorescence assay using BrdU antibody and Transwell assay. The oxidative stress ability of cells was determined by commercial kits. The levels of proteins related to cell proliferation and invasion were measured by western blotting. Results The level of miR-369-3p was significantly down-regulated in CRC tissues and cell lines, especially in SW480 cells (P<0.05). The expression of TCF4 was negatively correlated with that of miR-369-3p. High levels of miR-369-3p targeting TCF4 suppressed cell proliferation and downregulated the protein expression of Ki67 and PCNA (P<0.05). Overexpressed miR-369-3p binding TCF4 inhibited cell invasion and decreased the protein levels of vascular endothelial growth factor (VEGF) and E-cadherin (P<0.05). Furthermore, upregulation of miR-369-3p increased the activity of superoxide dismutase (SOD) while decreasing the content of malondialdehyde (MDA) and activity of lactate dehydrogenase (LDH) by blocking the expression of TCF4 (P<0.05). Conclusions MiR-369-3p inhibits the proliferation, invasion and oxidative stress of CRC cells by targeting TCF4, thus defining miR-369-3p as a potential target for the diagnosis and treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

In vitro study of miRNA-369-3p targeting TCF4 regulating the malignant biological behavior of colon cancer cells

Li,

Sun,

Granados-López

et al. 2023

J Gastrointest Oncol

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“…The complementary DNAs (cDNAs) of ITF2, β-catenin, and ubiquitin were cloned by reverse transcription and PCR using Pfu DNA polymerase, and the cDNAs were inserted into pcDNA, Myc-tagged, FLAG-tagged, HA-tagged, or FLAG/streptavidin-binding protein (SBP)-tagged vectors by blunt-end ligation. For transient gene silencing or protein expression, ~60% of confluent cells were transfected with small interfering RNAs or plasmids using the calcium phosphate method for HEK293T cells 64 . For other cells, Mirus TransIT-X2 (Mirus Bio, WI, USA) was used following the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Protein stabilization of ITF2 by NF-κB prevents colitis-associated cancer development

et al. 2023

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Chronic colonic inflammation is a feature of cancer and is strongly associated with tumorigenesis, but its underlying molecular mechanisms remain poorly understood. Inflammatory conditions increased ITF2 and p65 expression both ex vivo and in vivo, and ITF2 and p65 showed positive correlations. p65 overexpression stabilized ITF2 protein levels by interfering with the binding of Parkin to ITF2. More specifically, the C-terminus of p65 binds to the N-terminus of ITF2 and inhibits ubiquitination, thereby promoting ITF2 stabilization. Parkin acts as a E3 ubiquitin ligase for ITF2 ubiquitination. Intestinal epithelial-specific deletion of ITF2 facilitated nuclear translocation of p65 and thus increased colitis-associated cancer tumorigenesis, which was mediated by Azoxymethane/Dextran sulfate sodium or dextran sulfate sodium. Upregulated ITF2 expression was lost in carcinoma tissues of colitis-associated cancer patients, whereas p65 expression much more increased in both dysplastic and carcinoma regions. Therefore, these findings indicate a critical role for ITF2 in the repression of colitis-associated cancer progression and ITF2 would be an attractive target against inflammatory diseases including colitis-associated cancer.

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“…Additionally, research has shown that TGF-β1 can induce the proliferation and differentiation of chondrocytes by promoting FOXA1 expression [ 18 ]. Conversely, TGF-β1 can mediate EMT in lung cancer by suppressing FOXA1 expression [ 19 ]. Therefore, it is hypothesized that FOXA1 may play an important role in TGF-β1-induced EMT in GBC.…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 facilitates gallbladder carcinoma metastasis by regulating FOXA1 translation efficiency through m6A modification

Wu,

Ke,

Jiang

et al. 2024

Cell Death Dis

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TGF-β1 plays a pivotal role in the metastatic cascade of malignant neoplasms. N6-methyladenosine (m6A) stands as one of the most abundant modifications on the mRNA transcriptome. However, in the metastasis of gallbladder carcinoma (GBC), the effect of TGF-β1 with mRNA m6A modification, especially the effect of mRNA translation efficiency associated with m6A modification, remains poorly elucidated. Here we demonstrated a negative correlation between FOXA1 and TGF-β1 expression in GBC. Overexpression of FOXA1 inhibited TGF-β1-induced migration and epithelial-mesenchymal transition (EMT) in GBC cells. Mechanistically, we confirmed that TGF-β1 suppressed the translation efficiency of FOXA1 mRNA through polysome profiling analysis. Importantly, both in vivo and in vitro experiments showed that TGF-β1 promoted m6A modification on the coding sequence (CDS) region of FOXA1 mRNA, which was responsible for the inhibition of FOXA1 mRNA translation by TGF-β1. We demonstrated through MeRIP and RIP assays, dual-luciferase reporter assays and site-directed mutagenesis that ALKBH5 promoted FOXA1 protein expression by inhibiting m6A modification on the CDS region of FOXA1 mRNA. Moreover, TGF-β1 inhibited the binding capacity of ALKBH5 to the FOXA1 CDS region. Lastly, our study confirmed that overexpression of FOXA1 suppressed lung metastasis and EMT in a nude mice lung metastasis model. In summary, our research findings underscore the role of TGF-β1 in regulating TGF-β1/FOXA1-induced GBC EMT and metastasis by inhibiting FOXA1 translation efficiency through m6A modification.

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PGC1α Cooperates with FOXA1 to Regulate Epithelial Mesenchymal Transition through the TCF4-TWIST1

Cited by 6 publications

References 33 publications

In vitro study of miRNA-369-3p targeting TCF4 regulating the malignant biological behavior of colon cancer cells

In vitro study of miRNA-369-3p targeting TCF4 regulating the malignant biological behavior of colon cancer cells

Protein stabilization of ITF2 by NF-κB prevents colitis-associated cancer development

TGF-β1 facilitates gallbladder carcinoma metastasis by regulating FOXA1 translation efficiency through m6A modification

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