Identification of ZNF704 as a Novel Oncogene and an Independent Prognostic Marker in Chondrosarcoma

Chen, Changbao; Zhou, Hua; Zhang, Xiaolin; Liu, Zhongjun; Ma, Xiaofang

doi:10.2147/cmar.s313229

Cited by 3 publications

References 13 publications

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Stage-specific phenotypic and transcriptional alterations in keratinocytes exposed to acute and chronic blue light

Tonolli,

Nagahashi Marie,

Oba-Shinjo

et al. 2024

Preprint

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Despite evidence that visible light (VL) has similar effects on human skin as those of UVA, it is often viewed as harmless. High SPF sunscreen prevents erythema but can lead to overexposure to UVA and VL, with unknown consequences. To explore the impact of chronic blue light exposure, we irradiate keratinocytes under acute (3 irradiations, 50 J/cm2 each irradiation), intermediate (14 irradiations), and chronic (42 irradiations) blue-light exposures and followed phenotypic and gene expression changes. Chronically exposed keratinocytes exhibit increased nuclei area, chromatin alterations, higher proliferation, and apoptosis resistance, mirroring the consequences of chronic UVA exposure. While acute exposure upregulates keratinization and downregulates tissue repair and apoptosis genes, chronically exposed cells had upregulated genes involved with energy metabolism and oxidative phosphorylation, and downregulated genes were enriched for immune and inflammatory responses. Specific transcriptional factors were identified in the acute and chronic stages, some of them had been typically associated with UVB exposure. We identified changes in chronically irradiated keratinocytes similar to the changes characteristic of the malignant transformation, emphasizing the need for further research in the long-term impacts of blue light exposure on human skin.

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Stage-specific phenotypic and transcriptional alterations in keratinocytes exposed to acute and chronic blue light

Tonolli,

Nagahashi Marie,

Oba-Shinjo

et al. 2024

Preprint

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Zinc finger protein 468 up-regulation of TFAM contributes to the malignant growth and cisplatin resistance of breast cancer cells

Jia,

Wang,

et al. 2024

Cell Div

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Background Because of the progress on the diagnosis and treatment for patients with breast cancer (BC), the overall survival of the patients has been improved. However, a number of BC patients cannot benefit from the existing therapeutic strategies as the essential molecular events triggering the development of BC are not well understood. Previous studies have shown that abnormal expression of zinc finger proteins is involved in the development of various malignancies, whereas it remains largely unclear on their significance during the progression of BC. In this study, we aimed to explore the clinical relevance, cellular function and underlying mechanisms of zinc finger protein 468 (ZNF468) in BC. Methods The clinical relevance of ZNF468 and TFAM was analyzed based on TCGA database. Overexpression or knockdown of ZNF468 and TFAM were performed by transfecting the cells with overexpression plasmids and siRNAs, respectively. Overexpression and knockdown efficacy was checked by immunoblotting. CCK-8, colony formation, transwell and apoptosis experiments were conducted to check the cellular function of ZNF468 and TFAM. The content of mtDNA was measured by the indicated assay kit. The effects of cisplatin on BC cells were detected by CCK-8 and colony formation assays. The regulation of ZNF468 on TFAM was analyzed by RT-qPCR, immunoblotting, dual luciferase activity and ChIP-qPCR assays. Results ZNF468 was overexpressed in BC patients and inversely correlated with their prognosis. Based on overexpression and knockdown assays, we found that ectopic expression of ZNF468 was essential for the proliferation, growth and migration of BC cells. The expression of ZNF468 also negatively regulated the sensitivity of BC cells to the treatment of cisplatin. Mechanistically, ZNF468 potentiated the transcription activity of TFAM gene via direct binding on its promoter. Lastly, we demonstrated that ZNF468 up-regulation of TFAM was important for the growth, migration and cisplatin resistance in BC cells. Conclusion Our study indicates that ZNF468 promotes BC cell growth and migration via transcriptional activation of TFAM. ZNF468/TFAM axis can serve as the diagnostic and therapeutic target, as well as the predictor of cisplatin effectiveness in BC patients.

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Association of FBXW11 levels with tumor development and prognosis in chondrosarcoma

Chen

Zhou

Zhang

et al. 2022

CBM

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INTRODUCTION: The E3 ubiquitin ligase FBXW11 exerts an oncogenic or tumor suppressive function in a cellular context-dependent manner. However, the clinical significance and biological role of FBXW11 in chondrosarcoma have not been clearly characterized. This study focuses on the expression profile, prognostic value and biological function of FBXW11 in chondrosarcoma. METHODS: FBXW11 expression was analyzed by qRT-PCR and Western blot in six cases of chondrosarcoma specimens and the matched adjacent non-tumor tissues. The expression profile and prognostic value of FBXW11 were investigated in sixty-three cases of chondrosarcoma patients. Cell viability, colony formation, migration, invasion and apoptosis assays were further detected in SW1353 chondrosarcoma cells with restored FBXW11 expression. RESULTS: Downregulation of FBXW11 was remarkably detected in human chondrosarcoma specimens compared with the corresponding non-tumor tissues and benign cartilage tumors. Downregulated FBXW11 expression significantly correlated with high-grade chondrosarcoma and poor prognosis. Furthermore, FBXW11 was identified as an independent prognostic factor for the overall survival of chondrosarcoma patients. Restored expression of FBXW11 significantly suppressed chondrosarcoma cell growth and induced apoptosis. CONCLUSIONS: These findings establish that FBXW11 was markedly downregulated and recognized as an independent prognostic factor for patients with chondrosarcoma, and restored FBXW11 expression can suppress chondrosarcoma growth and induce apoptosis, highlighting a novel biological marker and potential therapeutic target against chondrosarcoma.

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Identification of ZNF704 as a Novel Oncogene and an Independent Prognostic Marker in Chondrosarcoma

Cited by 3 publications

References 13 publications

Stage-specific phenotypic and transcriptional alterations in keratinocytes exposed to acute and chronic blue light

Stage-specific phenotypic and transcriptional alterations in keratinocytes exposed to acute and chronic blue light

Zinc finger protein 468 up-regulation of TFAM contributes to the malignant growth and cisplatin resistance of breast cancer cells

Association of FBXW11 levels with tumor development and prognosis in chondrosarcoma

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