The Functions of DNA Damage Factor RNF8 in the Pathogenesis and Progression of Cancer

Zhou, Tingting; Yi, Fei; Wang, Zhuo; Guo, Qiqiang; Liu, Jingwei; Bai, Ning; Li, Xiaoman; Dong, Xiang Da; Ren, Ling; Cao, Liu; Song, Xiaoyu

doi:10.7150/ijbs.31972

Cited by 24 publications

(21 citation statements)

References 104 publications

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“…Additionally, increased expression of Pttg1 causes errors in chromosome segregation during mitosis due to increased genomic instability [ 76 ]. RNF8 functions in the signaling of DSBs through the mono-ubiquitination of H2A and H2B [ 77 , 78 ]. RNF8 deficiency has been associated with tumor development, probably due to increased genomic instability [ 79 ].…”

Section: Discussionmentioning

confidence: 99%

miR-27b-3p a Negative Regulator of DSB-DNA Repair

Peraza-Vega

Valverde

Rojas

2021

Genes

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Understanding the regulation of DNA repair mechanisms is of utmost importance to identify altered cellular processes that lead to diseases such as cancer through genomic instability. In this sense, miRNAs have shown a crucial role. Specifically, miR-27b-3 biogenesis has been shown to be induced in response to DNA damage, suggesting that this microRNA has a role in DNA repair. In this work, we show that the overexpression of miR-27b-3p reduces the ability of cells to repair DNA lesions, mainly double-stranded breaks (DSB), and causes the deregulation of genes involved in homologous recombination repair (HRR), base excision repair (BER), and the cell cycle. DNA damage was induced in BALB/c-3T3 cells, which overexpress miR-27b-3p, using xenobiotic agents with specific mechanisms of action that challenge different repair mechanisms to determine their reparative capacity. In addition, we evaluated the expression of 84 DNA damage signaling and repair genes and performed pathway enrichment analysis to identify altered cellular processes. Taken together, our results indicate that miR-27b-3p acts as a negative regulator of DNA repair when overexpressed.

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Section: Discussionmentioning

confidence: 99%

miR-27b-3p a Negative Regulator of DSB-DNA Repair

Peraza-Vega

Valverde

Rojas

2021

Genes

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“…The ubiquitin E3 ligase RNF8, which primarily functions in transducing DSB signals by conjugating ubiquitin to histones [22], has been reported to participate in tumorigenesis because RNF8 knockout mice develop various tumors spontaneously [44][45], indicating a negative role of RNF8 in tumorigenesis. However, RNF8 appears to have the opposite effect in tumor progression according to recent studies, because it promoted breast cancer proliferation and metastasis by affecting the Wnt/β-catenin pathway and activating the activity of transcription factors such as Twist and ERα [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

“…RING finger protein 8 (RNF8), which belongs to the RING finger E3 ligase family, is an essential factor for transducing DNA double-strand breaks (DSB) signaling [20][21][22]. It has been reported to be highly expressed in breast cancer and positively correlated with the progression of breast cancer by activating the Wnt/β-catenin pathway or enhancing the activity of Twist and estrogen receptor α (ERα) [23][24][25].…”

Section: Ivyspringmentioning

confidence: 99%

RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation

et al. 2020

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DNA damage signals transducer RING finger protein 8 (RNF8) is involved in maintaining genomic stability by facilitating the repair of DNA double-strand breaks (DSB) via ubiquitin signaling. By analyzing the TCGA database and colon cancer tissue microarrays, we found that the expression level of RNF8 was positively correlated with that of c-Myc in colon cancer, which were closely associated with poor survival of colon cancer patients. Furthermore, overexpressing and knocking down RNF8 increased and decreased the expression of c-Myc in colon cancer cells, respectively. In addition, RNF8 interacted with β-catenin and facilitated its nuclear translocation by conjugating K63 polyubiquitination on it. These observations suggested a de novo role of RNF8 in promoting the progression of colon cancer by inducing β-catenin-mediated c-Myc expression.

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“…The role of RNF8 in tumor development and progression exhibits a double-sided action, resulting in either tumor inhibition or promotion. In a mouse model, the downregulation or loss of RNF8 results in a significant increase of tumor incidence, including the incidence of leukemia in tumorigenesis of lymphoma (50%), thymoma (38%), mammary carcinoma (13%), skin tumor (13%) and sarcoma (13%) ( 30 ). A previous study has revealed that the expression levels of P53 are significantly increased in RNF8-knockout mice ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of the potential roles of ring finger protein 8 in TP53‑mutant breast cancer

et al. 2020

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Breast cancer is one of the malignant tumors with the highest mortality rate. With the development of precise treatment technology for cancer, numerous molecular targets have been identified and applied in the treatment of diseases. The present study investigated the potential role of ring finger protein 8 (RNF8) in TP53-mutant breast cancer and explored its possible mechanisms of action through a combination of bioinformatics techniques and cell biology. The results revealed that significantly different genes were expressed in RNF8-knockout mice sequencing data compared with in the control group in the presence of TP53 mutations. Downregulated genes were significantly enriched in several pathways of cell proliferation and apoptosis regulation, development and transcription regulation, while upregulated genes were mainly enriched in immune response-associated signaling pathways. Therefore, the consensus genes of the major signaling pathways were further analyzed, revealing that among patients with TP53 wild-type breast cancer, the prognosis of patients with low expression levels of fibroblast growth factor receptor 1, LIM homeobox 2 and EPH receptor B2 was improved compared with that of patients with high expression levels, while among patients with TP53-mutant breast cancer, there was no significant difference in survival status. In addition, among patients with TP53-mutant breast cancer, the prognosis of patients with high BR serine/threonine kinase 1 expression was significantly improved compared with that in patients with low expression. Finally, cell biology experiments demonstrated that in TP53-mutant breast cancer cells (HCC1937), inhibition of RNF8 significantly inhibited the proliferation of TP53-mutant HCC1937 cells and promoted their apoptosis. The present findings may enrich the understanding of the role of RNF8 and indicated that RNF8 may be used as a potential molecular target in TP53-mutant breast cancer, which may lead to the development of clinical treatment strategies.

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The Functions of DNA Damage Factor RNF8 in the Pathogenesis and Progression of Cancer

Cited by 24 publications

References 104 publications

miR-27b-3p a Negative Regulator of DSB-DNA Repair

miR-27b-3p a Negative Regulator of DSB-DNA Repair

RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation

Identification of the potential roles of ring finger protein 8 in TP53‑mutant breast cancer

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