Elevated double-strand break repair protein RAD50 predicts poor prognosis in hepatitis B virus-related hepatocellular carcinoma: A study based on Chinese high-risk cohorts

Liu, Wangrui; Xu, Wenhao; Chen, Yuyan; Gu, Liugen; Sun, Xiaolei; Qu, Yuanyuan; Zhang, Ye; Liu, Xiaojuan; Huang, Haiyang

doi:10.7150/jca.46703

Cited by 6 publications

(7 citation statements)

References 26 publications

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“…The average number of fluorescent foci per nucleus was significantly higher than that of control siRNA-treated cells (Figure 2 B) . To further demonstrate the role of SIRT7 in regulating chromosome stability, we performed RT-qPCR to analyze the effect of SIRT7 knockdown on mRNA levels of five chromosome stability-related genes, namely mitotic centromere-associated kinesin (MCAK) 31 , aurora kinase A (AURKA) 32 , brrier-to-autointegration factor (BANF1) 33 , RAD50 double strand break repair protein (RAD50) 34 , and breast cancer type 1 susceptibility protein (BRCA1) 35 . As shown in Figure 2 C , these genes were significantly downregulated when SIRT7 was knocked down, especially MACK, BANF1, and RAD50.…”

Section: Resultsmentioning

confidence: 99%

“…AURKA and BANF1 are associated with centrosome amplification, mitotic abnormalities, and chromosome instability 32 , 33 . DNA repair protein RAD50 expression causes cell instability, increasing the risk of DNA damage accumulation and malignant transformation 34 . Lose breast cancer type 1/2 susceptibility protein (BRCA1/2) activity causes genomic instability and chromosomal rearrangements 35 .…”

Section: Discussionmentioning

confidence: 99%

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SIRT7 Downregulation Promotes Breast Cancer Metastasis Via LAP2α-Induced Chromosomal Instability

Huo¹,

Chen²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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Chromosomal instability (CIN) plays an important role in the initiation and progression of carcinomas. However, the regulatory mechanism of metastasis mediated by CIN in breast cancer is not fully understood. Here, we aimed to demonstrate that the deregulation of SIRT7 and lamina-associated polypeptide 2α (LAP2α) critically contributes to CIN-induced metastasis in breast cancer. Expression of SIRT7 and chromosome stability-related genes was examined using western blotting, quantitative real-time PCR, immunohistochemistry, and immunofluorescence; functional significance of SIRT7 was examined using in vitro and in vivo models; and interaction between SIRT7 and LAP2α was assessed by co-inmunoprecipitation (Co-IP) assays. Doxorubicin (DOX) inhibited SIRT7 expression and enhanced CIN in breast cancer cells; SIRT7 deficiency led to CIN in breast cancer cells. Co-IP approach and immunohistochemistry demonstrated that SIRT7 interacted directly and positively with LAP2α and SIRT7 knockdown led to increased ubiquitination-dependent degradation of LAP2α and reduced protein levels of LAP2α, whereas LAP2α knockdown did not affect SIRT7 expression. In vitro and in vivo evidence revealed that SIRT7 promotes breast cancer metastasis through the SIRT7/LAP2α axis. In summary, SIRT7 interacts with LAP2α to regulate CIN and metastasis in breast cancer, and inhibition of SIRT7/LAP2α axis represents a potential therapeutic strategy for preventing breast cancer metastasis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

SIRT7 Downregulation Promotes Breast Cancer Metastasis Via LAP2α-Induced Chromosomal Instability

Huo¹,

Chen²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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“…For example, permeation-related ions allow tumor cells to invade by adjusting the shape and volume of cells. Besides, to adequately assess a biomarker’s ability to predict future risk of neoplastic progression, researchers have explored the prognostic and predictive immunological implications of cancers, such as glioma ( 14 ), liver carcinoma ( 15 ), and renal cell carcinoma ( 16 ). However, specifically, identifying highly sensitive and specific tumor markers is a challenge that needs to be solved for the early diagnosis of pan-cancer.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of the Oncogenic, Genomic Alteration, and Immunological Landscape of Cation-Chloride Cotransporters in Pan-Cancer

Wang

Liu

et al. 2022

Front. Oncol.

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BackgroundAssessing the phenotypic diversity underlying tumor progression requires the identification of variations in the respective molecular interaction in the tumor microenvironment (TME). Despite emerging studies focusing on the association between cation-chloride cotransporters (CCCs) and carcinogenesis, direct evidence that CCCs (KCC2 and NKCC1) mediate tumor progression in pan-cancer remains unclear.MethodsWe conducted a comprehensive assessment of the expression, DNA variation profiles, and prognostic and immunologic implications of CCCs based on a large-scale pan-cancer population, including 10,967 cancer patients from the Cancer Genome Atlas, 9,162 cancer patients from Genomics Expression Omnibus, 48,834 cancer patients from 188 independent studies, and 356 cancer patients from three real-world cohorts.ResultsIn this study, we first found that CCCs were highly expressed in most tumors, and prominently associated with prognosis. Kaplan–Meier analysis and Cox regression analysis revealed that KCC2 and NKCC1 significantly predicted survival for patients with pan-cancer, suggesting that CCCs have inconsistent tumorigenesis regulatory mechanisms in cancers. Next, we examined the DNA variation landscape of KCC2 and NKCC1 and their prognostic implications in pan-cancer. The results demonstrated that UCEC patients with somatic copy number variation (CNV) of NKCC1 received significantly better outcomes (p < 0.05). Besides emphasizing the clinical implications of CNV of CCCs for cancer patients, we found that NKCC1MUT could prominently prolong progression-free survival (p = 2.59e-04), disease-specific survival (p = 0.019), and overall survival (p = 0.034) compared with NKCC1WT cancer patients possibly via regulation of cell proliferation and oncogenic stress pathways. Additionally, KCC2 positively correlated with the levels of tumor-infiltrating macrophages and CD4+ T cells, but NKCC1 showed a significantly widely negative association with tumor-infiltrated lymphocytes, suggesting an immune-excluded TME in cancers. Similarly, expression of KCC2, rather than NKCC1, was positively correlated with the immune checkpoint molecules, indicating its role as an immune regulator in a wide variety of cancers. Finally, to verify our hypothesis and altered expression of CCCs, we performed IHC analysis and revealed the staining distribution in tumor and adjacent normal tissues of glioma, clear cell renal cell carcinoma, papillary cell renal cell carcinoma, and hepatocellular and breast cancer from three real-world cohorts, and validated prominently prognostic implications of CCCs in patients with clear cell renal cell carcinoma.ConclusionThis study first comprehensively investigated the molecular and clinical role of CCCs, and illustrated the significant association among KCC2/NKCC1 expression, DNA variation profiles prognosis, and TME of pan-cancer. The pan-cancer findings provided an in-depth understanding of potential oncogenic and immunologic of differential expression and DNA alteration of KCC2/NKCC1 cancers.

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“…However, improvements in the prognosis of liver cancer remain challenging. The therapeutic effects of first-line HCC drugs such as sorafenib are poor ( Galun et al, 2017 ; Saffo and Taddei, 2019 ), and no prognostic classification and markers have been identified to provide guidance for personalized treatment ( Liu et al, 2020a ; Zhao et al, 2021a ; Zhao et al, 2021b ). Therefore, a new treatment strategy is required to predict the prognosis of liver cancer.…”

Section: Introductionmentioning

confidence: 99%

Integrating machine learning to construct aberrant alternative splicing event related classifiers to predict prognosis and immunotherapy response in patients with hepatocellular carcinoma

Liu

Zhao

et al. 2022

Front. Pharmacol.

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Introduction: In hepatocellular carcinoma (HCC), alternative splicing (AS) is related to tumor invasion and progression.Methods: We used HCC data from a public database to identify AS subtypes by unsupervised clustering. Through feature analysis of different splicing subtypes and acquisition of the differential alternative splicing events (DASEs) combined with enrichment analysis, the differences in several subtypes were explored, cell function studies have also demonstrated that it plays an important role in HCC.Results: Finally, in keeping with the differences between these subtypes, DASEs identified survival-related AS times, and were used to construct risk proportional regression models. AS was found to be useful for the classification of HCC subtypes, which changed the activity of tumor-related pathways through differential splicing effects, affected the tumor microenvironment, and participated in immune reprogramming.Conclusion: In this study, we described the clinical and molecular characteristics providing a new approach for the personalized treatment of HCC patients.

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Elevated double-strand break repair protein RAD50 predicts poor prognosis in hepatitis B virus-related hepatocellular carcinoma: A study based on Chinese high-risk cohorts

Cited by 6 publications

References 26 publications

SIRT7 Downregulation Promotes Breast Cancer Metastasis Via LAP2α-Induced Chromosomal Instability

SIRT7 Downregulation Promotes Breast Cancer Metastasis Via LAP2α-Induced Chromosomal Instability

Comprehensive Analysis of the Oncogenic, Genomic Alteration, and Immunological Landscape of Cation-Chloride Cotransporters in Pan-Cancer

Integrating machine learning to construct aberrant alternative splicing event related classifiers to predict prognosis and immunotherapy response in patients with hepatocellular carcinoma

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