Aberrant Expression of RAD52, Its Prognostic Impact in Rectal Cancer and Association with Poor Survival of Patients

Ho, Vincent; Chung, Liping; Singh, Amandeep; Lea, Vivienne; Abubakar, Askar; Lim, Stephanie; Chua, Wei; Ng, Wan; Lee, Mark; Roberts, Tara L.; Souza, Paul de; Lee, Cheok Soon

doi:10.3390/ijms21051768

Cited by 15 publications

(16 citation statements)

References 61 publications

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“…Several studies reported an association between high RAD52 expression level in tumor samples with poor patient prognosis and disease prognosis ( Jewell et al, 2010 ; Lieberman and You 2017 ; Ho et al, 2020 ). In a study of cancer cells containing an inactivated RECQL4 gene and upregulated RAD52, inhibition of RAD52 sensitized the cancer cells to ionizing radiation ( Kohzaki et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

RAD52: Paradigm of Synthetic Lethality and New Developments

et al. 2021

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DNA double-strand breaks and inter-strand cross-links are the most harmful types of DNA damage that cause genomic instability that lead to cancer development. The highest fidelity pathway for repairing damaged double-stranded DNA is termed Homologous recombination (HR). Rad52 is one of the key HR proteins in eukaryotes. Although it is critical for most DNA repair and recombination events in yeast, knockouts of mammalian RAD52 lack any discernable phenotypes. As a consequence, mammalian RAD52 has been long overlooked. That is changing now, as recent work has shown RAD52 to be critical for backup DNA repair pathways in HR-deficient cancer cells. Novel findings have shed light on RAD52’s biochemical activities. RAD52 promotes DNA pairing (D-loop formation), single-strand DNA and DNA:RNA annealing, and inverse strand exchange. These activities contribute to its multiple roles in DNA damage repair including HR, single-strand annealing, break-induced replication, and RNA-mediated repair of DNA. The contributions of RAD52 that are essential to the viability of HR-deficient cancer cells are currently under investigation. These new findings make RAD52 an attractive target for the development of anti-cancer therapies against BRCA-deficient cancers.

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Section: Introductionmentioning

confidence: 99%

RAD52: Paradigm of Synthetic Lethality and New Developments

et al. 2021

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“…RAD52 promotes cell proliferation capacity and mobility in HCC [ 31 ]. Elevated RAD52 expression is related to worse DFS in patients with rectal cancer [ 32 ]. In this paper, we confirmed that the progression of OC cells was reduced dramatically after RAD52 knockdown.…”

Section: Discussionmentioning

confidence: 99%

SF3B4 promotes ovarian cancer progression by regulating alternative splicing of RAD52

Diao

Wang

et al. 2022

Cell Death Dis

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Many studies have proven that splicing factors are crucial for human malignant tumor development. However, as a classical splicing factor, the expression of SF3B4 is not clear, and its biological function needs to be further clarified in ovarian cancer (OC). We determined that SF3B4 was obviously upregulated and its high expression was associated with poor prognosis in OC patients. In vitro and in vivo assays suggested that SF3B4 overexpression promoted OC cell proliferation and mobility, and downregulation of SF3B4 had the opposite effect. Further studies found that miR-509–3p decreased SF3B4 mRNA expression by binding to the 3’ -UTR of SF3B4 directly. Importantly, we revealed that RAD52 was a potential target of SF3B4 through alternative splicing events analysis. Loss of SF3B4 led to decreased expression of RAD52, owing to intron 8 retention and generation of premature termination codons. Moreover, decreased expression of RAD52 partially counteracted the tumor-promoting effect of SF3B4 overexpression. In conclusion, our results suggested that SF3B4, negatively regulated by miR-509–3p, promoted OC progression through effective splicing of RAD52. Therefore, SF3B4 may be a promising biomarker and effective therapeutic target for OC.

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“…IL7 may play an anti-tumor role through apoptosis pathway [48]In addition, IL7 can also enhance the anti-tumor immunity by combining other factors to enhance the function of immune cells (46). The protein encoded by the RAD52 gene is a DNA-binding protein that participates in the DNA repair process, Double-strand breaks are the main cause of tumor cell death, and the RAD52 protein plays an important role in the repair of double-strand break damage (33,47). In addition, the RAD52 protein is also essential for DNA synthesis during mitosis (48).…”

Section: Discussionmentioning

confidence: 99%

Effect of Aging-Related Genes on the Prognosis of Colon Cancer

Liu

Gong

Huang

et al. 2021

Preprint

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Background:Colon cancer is a common malignant cancer with high incidence and poor prognosis. Cell senescence and apoptosis are important mechanisms of tumor occurrence and development, in which aging-related genes(ARGs) play an important role. This study aimed to establish a prognostic risk model based on ARGs for diagnosis and prognosis prediction of colon cancer .Methods: We downloaded transcriptome data and clinical information of colon cancer patients from the Cancer Genome Atlas(TCGA) database and the microarray dataset(GSE39582) from the Gene Expression Omnibus(GEO) database. Univariate COX, least absolute shrinkage and selection operator(LASSO) regression algorithm and multivariate COX regression analysis were used to construct a 6-ARG prognosis model and calculated the riskScore. The prognostic signatures is validated by internal validation cohort and external validation cohort(GSE39582).In addition, functional enrichment pathways and immune microenvironment of aging-related genes(ARGs) were also analyzed. We also analyzed the correlation between rsikScore and clinical features and constructed a nomogram based on riskScore. We are the first to construct prognostic nomogram based on ARGs.Results: Through univariate COX,LASSO regression algorithm and multivariate COX regression analysis,6 prognostic ARGs (PDPK1,RAD52,GSR,IL7,BDNF and SERPINE1) were screened out and riskScore was constructed. We have verified that riskScore has good prognostic value in both internal validation cohort and external validation cohort. Pathway enrichment and immunoanalysis of ARGs provide a direction for the treatment of colon cancer patients. We also found that riskScore was closely related to the clinical characteristics of patients. Based on riskScore and related clinical features, we constructed a nomogram, which has good predictive performance.Conclusion: The 6-ARG prognostic signature we constructed has a certain clinical predictive ability. Its riskScore is also closely related to clinical characteristics, and nomogram based on this has stronger predictive ability than a single indicator. ARGs and the nomogram we constructed may provide a promising treatment for colon cancer patients.

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Aberrant Expression of RAD52, Its Prognostic Impact in Rectal Cancer and Association with Poor Survival of Patients

Cited by 15 publications

References 61 publications

RAD52: Paradigm of Synthetic Lethality and New Developments

RAD52: Paradigm of Synthetic Lethality and New Developments

SF3B4 promotes ovarian cancer progression by regulating alternative splicing of RAD52

Effect of Aging-Related Genes on the Prognosis of Colon Cancer

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