<scp>CXXC</scp>5 expression in prostate cancer: implications for cancer progression

Benedetti, Inés; Marzo, Angelo M. De; Geliebter, Jan; Reyes, Niradiz

doi:10.1111/iep.12241

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…37,38 In recent years, CXXC5 was found to be abnormally expressed in various tumor diseases. Meanwhile, there were differences in CXXC5 expression between different cancers: increased CXXC5 expression was verified in prostate cancer, breast cancer and endometrial cancer, 25,39,40 while the expression of CXXC5 was decreased in human malignant peripheral nerve sheath tumors. 37 Sui and colleagues discovered that CXXC5 might be downregulated in GC through microarray analysis.…”

Section: Discussionmentioning

confidence: 99%

<p>The KN Motif and Ankyrin Repeat Domains 1/CXXC Finger Protein 5 Axis Regulates Epithelial-Mesenchymal Transformation, Metastasis and Apoptosis of Gastric Cancer via Wnt Signaling</p>

Chen

Wang

et al. 2020

OTT

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Background: Emerging research indicates that CXXC finger protein 5 (CXXC5) is involved in the development of various cancers. Besides, KN motif and ankyrin repeat domains 1 (KANK1) was proved as a tumor suppressor in multiple cancers. Our study aimed to illustrate the functional role and mechanism of CXXC5 and KANK1 in gastric cancer (GC) pathogenesis. Methods: The tissues of 55 GC patients and six GC cell lines were used to investigate CXXC5 and KANK1 expression using RT-qPCR. Western blot assay was conducted to measure the protein levels of CXXC5, KANK1, epithelial-mesenchymal transformation (EMT) proteins (Vimentin, E-cadherin) and Wnt signaling proteins (β-catenin, Axin2). The correlation between KANK1 and CXXC5 was estimated by Pearson's correlation analysis. The results of Transwell assays showed the migration and invasion abilities of GC cells, while the apoptosis rate was detected by flow cytometry. Results: The expressions of CXXC5 and KANK1 were both decreased in GC tissues and cells, compared with the normal ones (P < 0.01). Overexpressing CXXC5 significantly induced apoptosis (P < 0.05) and inhibited EMT, migration (P < 0.05) and invasion (P < 0.01) in GC cells. Wnt/β-catenin/Axin2 signaling was suppressed by CXXC5 overexpression, and activating Wnt/β-catenin/Axin2 signaling reversed the effects of CXXC5. The expression of KANK1 was found to be positively correlated with CXXC5 (r 2 = 0.4024). KANK1 presented similar effects with CXXC5 on GC cells; however, silencing CXXC5 or activating Wnt/β-catenin/Axin2 signaling antagonized the effects of KANK1 overexpression on EMT and apoptosis in GC (P < 0.05). Conclusion: Our study suggested that CXXC5 was downregulated in GC and participated in EMT and apoptosis regulations via the Wnt/β-catenin/Axin2 pathway. Besides, the decreased expression of CXXC5 in GC was caused by KANK1 dysregulation.

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Section: Discussionmentioning

confidence: 99%

<p>The KN Motif and Ankyrin Repeat Domains 1/CXXC Finger Protein 5 Axis Regulates Epithelial-Mesenchymal Transformation, Metastasis and Apoptosis of Gastric Cancer via Wnt Signaling</p>

Chen

Wang

et al. 2020

OTT

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“…There are few studies on pulmonary fibrosis in CXXC5 locally and abroad, and the role and mechanism of CXXC5 in pulmonary fibrosis are unclear. CXXC5 was first found in myeloid leukemia [16,17], and later, CXXC5 overexpression was found in breast cancer, prostate cancer [18,19], and other malignant diseases. Besides, CXXC5 overexpression was associated with the poor prognosis of malignant tumors.…”

Section: Biomed Research Internationalmentioning

confidence: 99%

“…13 BioMed Research International later, CD40 was found to be expressed in other nonhematopoietic cells, including lung fibroblasts [18,19], indicating that CD40/CD40L may regulate the function of fibroblasts. CD40 on the surface of fibroblasts can bind to CD40L, promote the proliferation of fibroblasts and possibly the production of IL-6 and IL-8 by activating the NF-κB pathway, and express ICAM and VCAM-1.…”

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confidence: 99%

CXXC5 Attenuates Pulmonary Fibrosis in a Bleomycin-Induced Mouse Model and MLFs by Suppression of the CD40/CD40L Pathway

Cheng

Wang

Feng

et al. 2020

BioMed Research International

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Objective. To investigate the role of CXXC5 and the CD40/CD40L pathway in lung fibrosis. Methods. (1) We constructed mouse models of bleomycin-induced pulmonary fibrosis and transfected them with a CXXC5 overexpression vector to evaluate the severity of pulmonary fibrosis. (2) Mouse lung fibroblast (MLF) models stably overexpressed or knockout of CXXC5 vector were constructed. After transforming growth factor-β1 (TGF-β1) stimulation, we examined the proliferation and apoptosis of the MLF model and evaluated the expression of mesenchymal markers and the CXXC5/CD40/CD40L pathway. Results. (1) Compared with other groups, the overexpressed CXXC5 group had less alveolar structure destruction, thinner alveolar septum, and lower Ashcroft score. (2) In bleomycin-induced mice, the expression of CD40 and CD40L increased at both transcriptional and protein levels, and the same changes were observed in α-smooth muscle actin (α-SMA) and collagen type I (Colla I). After upregulation of CXXC5, the increase in CD40, CD40L, α-SMA, and Colla I was attenuated. (3) Stimulated with TGF-β1, MLF proliferation was activated, apoptosis was suppressed, and the expression of CD40, CD40L, α-SMA, and Colla I was increased at both transcriptional and protein levels. After upregulation of CXXC5, these changes were attenuated. Conclusion. CXXC5 inhibits pulmonary fibrosis and transformation to myofibroblasts by negative feedback regulation of the CD40/CD40L pathway.

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CXXC5 as an unmethylated CpG dinucleotide binding protein contributes to estrogen-mediated cellular proliferation

Ayaz

Razizadeh

Yaşar

et al. 2020

Sci Rep

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Evidence suggests that the CXXC type zinc finger (ZF-CXXC) protein 5 (CXXC5) is a critical regulator/integrator of various signaling pathways that include the estrogen (E2)-estrogen receptor α (ERα). Due to its ZF-CXXC domain, CXXC5 is considered to be a member of the ZF-CXXC family, which binds to unmethylated CpG dinucleotides of DNA and through enzymatic activities for DNA methylation and/or chromatin modifications generates a chromatin state critical for gene expressions. Structural/functional features of CXXC5 remain largely unknown. CXXC5, suggested as transcription and/or epigenetic factor, participates in cellular proliferation, differentiation, and death. To explore the role of CXXC5 in E2-ERα mediated cellular events, we verified by generating a recombinant protein that CXXC5 is indeed an unmethylated CpG binder. We uncovered that CXXC5, although lacks a transcription activation/repression function, participates in E2-driven cellular proliferation by modulating the expression of distinct and mutual genes also regulated by E2. Furthermore, we found that the overexpression of CXXC5, which correlates with mRNA and protein levels of ERα, associates with poor prognosis in ER-positive breast cancer patients. Thus, CXXC5 as an unmethylated CpG binder contributes to E2-mediated gene expressions that result in the regulation of cellular proliferation and may contribute to ER-positive breast cancer progression.

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CXXC5 expression in prostate cancer: implications for cancer progression

Cited by 7 publications

References 23 publications

<p>The KN Motif and Ankyrin Repeat Domains 1/CXXC Finger Protein 5 Axis Regulates Epithelial-Mesenchymal Transformation, Metastasis and Apoptosis of Gastric Cancer via Wnt Signaling</p>

<p>The KN Motif and Ankyrin Repeat Domains 1/CXXC Finger Protein 5 Axis Regulates Epithelial-Mesenchymal Transformation, Metastasis and Apoptosis of Gastric Cancer via Wnt Signaling</p>

CXXC5 Attenuates Pulmonary Fibrosis in a Bleomycin-Induced Mouse Model and MLFs by Suppression of the CD40/CD40L Pathway

CXXC5 as an unmethylated CpG dinucleotide binding protein contributes to estrogen-mediated cellular proliferation

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