Downregulation of ZNF395 Drives Progression of Pancreatic Ductal Adenocarcinoma through Enhancement of Growth Potential

Kurogi, Shusaku; Hijiya, Naoki; Hidano, Shinya; Sato, Seiya; Uchida, Tomohisa; Tsukamoto, Yoshiyuki; Nakada, Chisato; Yada, Kazuhiro; Hirashita, Teijiro; Ito, Masafumi; Murakami, Kazunari; Takahashi, Naohiko; Kobayashi, Takashi; Moriyama, Masatsugu

doi:10.1159/000514593

Cited by 3 publications

(3 citation statements)

References 23 publications

(31 reference statements)

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“…The KANK family plays roles in actin cytoskeleton organization and cell motility; however, KANK3 functions are not well understood, and KANK3 might act as a tumor suppressor [ 72 ]. A recent study proposed that ZNF395 is a novel tumor suppressor gene [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells

et al. 2022

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Butyrate is produced in the rumen from microbial fermentation and is related to several functions, including cell differentiation and proliferation. Butyrate supplementation in calves can accelerate rumen development. DNA-protein interactions, such as the CCCTC-binding factor (CTCF), play essential roles in chromatin organization and gene expression regulation. Although CTCF-binding sites have been identified recently in cattle, a deeper characterization, including differentially CTCF-binding sites (DCBS), is vital for a better understanding of butyrate’s role in the chromatin landscape. This study aimed to identify CTCF-binding regions and DCBS under a butyrate-induced condition using ChIP-seq in bovine cells; 61,915 CTCF peaks were identified in the butyrate and 51,347 in the control. From these regions, 2265 DCBS were obtained for the butyrate vs. control comparison, comprising ~90% of induced sites. Most of the butyrate DCBS were in distal intergenic regions, showing a potential role as insulators. Gene ontology enrichment showed crucial terms for the induced DCBS, mainly related to cellular proliferation, cell adhesion, and growth regulation. Interestingly, the ECM-receptor interaction pathway was observed for the induced DCBS. Motif enrichment analysis further identified transcription factors, including CTCF, BORIS, TGIF2, and ZIC3. When DCBS was integrated with RNA-seq data, putative genes were identified for the repressed DCBS, including GATA4. Our study revealed promising candidate genes in bovine cells by a butyrate-induced condition that might be related to the regulation of rumen development, such as integrins, keratins, and collagens. These results provide a better understanding of the function of butyrate in cattle rumen development and chromatin landscape regulation.

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Section: Discussionmentioning

confidence: 99%

Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells

et al. 2022

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“…Two thousand cells in 100 μL of medium were cultured in a 96‐well tissue culture plate (Corning) for the indicated periods at 37°C in 5% CO 2 . Proliferation was analyzed by MTS assay, as described previously 19 …”

Section: Methodsmentioning

confidence: 99%

Involvement of clusterin expression in the refractory response of pancreatic cancer cells to a MEK inhibitor

et al. 2023

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Constitutive activation of the mitogen‐activated protein kinase (MAPK) signaling pathway is essential for tumorigenesis of pancreatic ductal adenocarcinoma (PDAC). To date, however, almost all clinical trials of inhibitor targeting this pathway have failed to improve the outcome of patients with PDAC. We found that implanted MIA Paca2, a human PDAC cell line sensitive to a MAPK inhibitor, PD0325901, became refractory within a week after treatment. By comparing the expression profiles of MIA Paca2 before and after acquisition of the refractoriness to PD0325901, we identified clusterin (CLU) as a candidate gene involved. CLU was shown to be induced immediately after treatment with PD0325901 or expressed primarily in more than half of PDAC cell lines, enhancing cell viability by escaping from apoptosis. A combination of PD0325901 and CLU downregulation was found to synergistically or additively reduce the proliferation of PDAC cells. In surgically resected PDAC tissues, overexpression of CLU in cancer cells was observed immunohistochemically in approximately half of the cases studied. Collectively, our findings highlight the mechanisms responsible for the rapid refractory response to MEK inhibitor in PDAC cells, suggesting a novel therapeutic strategy that could be applicable to patients with PDAC using inhibitor targeting the MAPK signaling pathway and CLU.

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“…No mycoplasma contamination was detected by PCR in any of the cell lines during the study. For establishment of SNU-C5 cells inducibly expressing VSNL1, we used the pTRIPZ lentiviral vector (Thermo Fisher Scientific, Waltham, MA, USA), which encodes red fluorescent protein (RFP) whose expression is induced in the presence of doxycycline [16]. This vector, or the modified version in which the RFP gene was substituted by cDNA encoding the whole amino acid sequence of VSNL1, was transduced into SNU-C5 cells using lipofectamine 2000 (Thermo Fisher Scientific).…”

Section: Cell Linesmentioning

confidence: 99%

Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis

Aiba,

Hijiya,

Akagi

et al. 2023

Pathobiology

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Introduction: We have previously reported that overexpression of VSNL1 (Visinin-like protein 1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis. Methods: Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT116 were identified using transcriptome and gene set enrichment analyses. Results: VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT116 cells. Conclusion: VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability.

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Downregulation of ZNF395 Drives Progression of Pancreatic Ductal Adenocarcinoma through Enhancement of Growth Potential

Cited by 3 publications

References 23 publications

Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells

Butyrate Induces Modifications of the CTCF-Binding Landscape in Cattle Cells

Involvement of clusterin expression in the refractory response of pancreatic cancer cells to a MEK inhibitor

Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis

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