GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process [Erratum]

Shen, Jingang; Lv, Xianbao; Zhang, Lei

doi:10.2147/ott.s283751

Cited by 4 publications

(8 citation statements)

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“…2e, f), and significantly enriched for transcription factors (16.45%, Fisher’s Exact Test odds ratio = 3.12, p value = 5.192e-07) defined by Lambert et al 70 , consisting of several FOX family and Zinc finger family members (Supplementary Table 4). Those also include GRHL2 , which was previously identified as anti-oncogene in bladder carcinoma by regulating the expression of ZEB1 gene thus preventing EMT both in cell lines and tissue samples 71 . In addition, KDM5B, which is a H3K4 demethylase 72 and regulated by NMIBC specific enhancers, is also implicated in progression of bladder carcinoma 73 .…”

Section: Resultsmentioning

confidence: 99%

FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer

Sozeri

Yilmaz

Kisim

et al. 2021

Preprint

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SUMMARYBladder cancer is mostly present in the form of urothelium carcinoma, causing over 150.000 deaths each year. Its histopathological classification as muscle invasive (MIBC) and non-muscle invasive (NMIBC) is the most prominent aspect, affecting the prognosis and progression of this disease. In this study, we defined the active regulatory landscape of MIBC and NMIBC cell lines using H3K27ac-seq and used an integrative data approach to combine our findings with existing data. Our analysis revealed FRA1 and FLI1 as the two critical transcription factors differentially regulating MIBC regulatory landscape. Importantly, we show that FRA1 and FLI1 regulate the genes involved in epithelial cell migration and cell junction organization. Knock-down of FRA1 and FLI1 in MIBC revealed the downregulation of several EMT-related genes such as MAP4K4 and FLOT1. Further, ChIP-SICAP performed for FRA1 and FLI1 enabled us to infer chromatin binding partners of these two transcription factors and link this information with their target genes, providing a comprehensive regulatory circuit for the genes implicated in invasive ability of the bladder cancer cells. Finally, for the first time we show that knock-down of FRA1 and FRA1-FLI1 double knock-down results in significant reduction of invasion capacity of MIBC cells towards muscle microenvironment using IC-CHIP assays. Our results collectively highlight the role of these two transcription factors in invasive characteristics of bladder cancer in selection and design of targeted options for treatment of MIBC.

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Section: Resultsmentioning

confidence: 99%

FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer

Sozeri

Yilmaz

Kisim

et al. 2021

Preprint

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“…Previous studies have reported that Grhl2 is involved in the EMT process of tumor cells by binding to ZEB1 promoter to inhibit its transcription. 32 However, this study also found that ZEB1 was not involved in Grhl2-/RBM25-regulated cell migration and EMT. Next, we will further investigate how Grhl2 regulates the EMT of trophoblasts during PE.…”

Section: Discussionmentioning

confidence: 51%

“…Grhl2 inhibits bladder cancer cell proliferation and inhibits EMT process by downregulating ZEB1 expression. 32 Our group previous study revealed that Grhl2 was highly expressed in PE placenta, and circTNRC18-induced miR-762 inhibited upregulation of Grhl2, leading to trophoblast migration and EMT. 16 In this study, we found that Grhl2 was involved in RBM25-regulated trophoblast cells migration, invasion, and EMT.…”

Section: Discussionmentioning

confidence: 93%

“…31 Emerging studies have shown that Grhl2 is a negative regulator of cellular EMT process. 32 Yang et al 25 reported that Grhl2 depresses the progression and metastasis of colorectal cancer by inhibiting epithelial-mesenchymal transition. Grhl2 inhibits bladder cancer cell proliferation and inhibits EMT process by downregulating ZEB1 expression.…”

Section: Discussionmentioning

confidence: 99%

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RBM25 induces trophoblast epithelial-mesenchymal transition and preeclampsia disorder by enhancing the positive feedback loop between Grhl2 and RBM25

Zhang,

Chen,

Yang

et al. 2023

Exp Biol Med (Maywood)

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Defects in migration and invasion caused by dysregulation of trophoblast epithelial-mesenchymal transformation (EMT) are one of the key factors in the pathogenesis of preeclampsia (PE). RNA-binding motif protein 25 (RBM25) is an RNA-binding protein involved in a variety of cellular processes, including cell proliferation, apoptosis, cell migration and invasion, and EMT. However, the expression and function of RBM25 in placental of PE remain unclear. In this study, we reveal that the expression of RBM25 is significantly elevated in PE placental tissue. RBM25 depletion and over-expression in trophoblast cells increase and decrease, respectively, cell migration and invasion by regulating EMT marker E-cadherin and Vimentin expression. Mechanistically, Grhl2 is involved in RBM25-regulated trophoblast cell migration, invasion, and EMT through RBM25-facilitated mRNA stabilization. Furthermore, the upregulation of Grhl2 enhances the expression of RBM25 through transcription and forms a positive feedback regulation in the progression of PE. These findings suggest that upregulation of RBM25 induces dysregulation of trophoblast EMT by enhancing positive feedback regulation of Grhl2 and RBM25, leading to defects in cell migration and invasion. Targeting this newly identified regulatory axis may provide benefits in the prevention and treatment of PE.

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“…This regulation controls the anterior migration of gastrulation in embryogenesis [215] and contributes to the tumor invasion, stem-like motility and chemoresistance [216]. In addition, not only SNAIL1, the related EMT transcription factors such as ZEB1 and twist1 were also found to be regulated by MET-related dominant molecules, the OVOL1/2 [217][218][219], and GRHL2 [220,221], and such factors were involved in wound healing and embryogenesis as well [222][223][224]. According to the report by Pienta et al, both OVOL1/2 serve as negative regulators in prostate or breast cancer, in which overexpression of OVOL1 or OVOL2 can decrease ZEB1 to restrict cells EMT, consequently suppressing metastasis [225].…”

Section: Upstream Regulators Contribute To Determining the Emt/met In Cancersmentioning

confidence: 99%

Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis

Hsu

Chang

et al. 2021

Biomedicines

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Epithelial and mesenchymal transition mechanisms continue to occur during the cell cycle and throughout human development from the embryo stage to death. In embryo development, epithelial-mesenchymal transition (EMT) can be divided into three essential steps. First, endoderm, mesoderm, and neural crest cells form, then the cells are subdivided, and finally, cardiac valve formation occurs. After the embryonic period, the human body will be subjected to ongoing mechanical stress or injury. The formation of a wound requires EMT to recruit fibroblasts to generate granulation tissues, repair the wound and re-create an intact skin barrier. However, once cells transform into a malignant tumor, the tumor cells acquire the characteristic of immortality. Local cell growth with no growth inhibition creates a solid tumor. If the tumor cannot obtain enough nutrition in situ, the tumor cells will undergo EMT and invade the basal membrane of nearby blood vessels. The tumor cells are transported through the bloodstream to secondary sites and then begin to form colonies and undergo reverse EMT, the so-called “mesenchymal-epithelial transition (MET).” This dynamic change involves cell morphology, environmental conditions, and external stimuli. Therefore, in this manuscript, the similarities and differences between EMT and MET will be dissected from embryonic development to the stage of cancer metastasis.

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GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process [Erratum]

Cited by 4 publications

References 0 publications

FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer

FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer

RBM25 induces trophoblast epithelial-mesenchymal transition and preeclampsia disorder by enhancing the positive feedback loop between Grhl2 and RBM25

Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis

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