Human RecQL4 helicase plays multifaceted roles in the genomic stability of normal and cancer cells

Mo, Dong‐Liang; Zhao, Yongliang; Balajee, Adayabalam S.

doi:10.1016/j.canlet.2017.10.021

Cited by 46 publications

(50 citation statements)

References 80 publications

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“…Germline mutations in the BLM , WRN and RECQL4 genes cause the hereditary cancer predisposition syndromes Bloom syndrome, Werner syndrome and Rothmund–Thomson syndrome (RTS) type II, respectively . RECQL4 mutations are also associated with Baller–Gerold syndrome (BGS) and RAPADILINO syndrome . RTS patients have higher risk of osteosarcoma (~30%) than lymphoma (~7%), while RAPADILINO syndrome patients have higher risk of lymphoma (~27%) than osteosarcoma (~13%) for unknown reason .…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, there are currently no effective therapies for these cancers developed by patients presenting with RECQL4‐associated diseases . Dysregulation of human RECQL4 is also associated with several cancers . RECQL4 has unique characteristics among the RECQ helicase family members .…”

Section: Introductionmentioning

confidence: 99%

“…S2). The RECQL4 mutations that cause RTS are mainly located around the helicase domain at exons 8–14 . Hence, the RECQL4 C‐terminal region, including the helicase domain, is dispensable for viability in vertebrates .…”

Section: Introductionmentioning

confidence: 99%

“…16 RECQL4 mutations are also associated with Baller-Gerold syndrome (BGS) and RAPADILINO syndrome. 17 RTS patients have higher risk of osteosarcoma (~30%) than lymphoma (~7%), while RAPADILINO syndrome patients have higher risk of lymphoma (~27%) than osteosarcoma (~13%) for unknown reason. 18 Unfortunately, there are currently no effective therapies for these cancers developed by patients presenting with RECQL4-associated diseases.…”

Section: Introductionmentioning

confidence: 99%

“…19,20 Dysregulation of human RECQL4 is also associated with several cancers. 17 RECQL4 has unique characteristics among the RECQ helicase family members. 16 The putative yeast Sld2 domain, which is indispensable for replication initiation and viability, is located at the N-terminal region of RECQL4.…”

Section: Introductionmentioning

confidence: 99%

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Human RECQL4 represses the RAD52‐mediated single‐strand annealing pathway after ionizing radiation or cisplatin treatment

Kohzaki

Ootsuyama

Sun

et al. 2019

Intl Journal of Cancer

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Ionizing radiation (IR) and cisplatin are frequently used cancer treatments, although the mechanisms of error‐prone DNA repair‐mediated genomic instability after anticancer treatment are not fully clarified yet. RECQL4 mutations mainly in the C‐terminal region of the RECQL4 gene lead to the cancer‐predisposing Rothmund–Thomson syndrome, but the function of RECQL4ΔC (C‐terminus deleted) in error‐prone DNA repair remains unclear. We established several RECQL4ΔC cell lines and found that RECQL4ΔC cancer cells, but not RECQL4ΔC nontumorigenic cells, exhibited IR/cisplatin hypersensitivity. Notably, RECQL4ΔC cancer cells presented increased RPA2/RAD52 foci after cancer treatments. RECQL4ΔC HCT116 cells exhibited increased error‐prone single‐strand annealing (SSA) activity and decreased alternative end‐joining activities, suggesting that RECQL4 regulates the DNA repair pathway choice at double‐strand breaks. RAD52 depletion by siRNA or RAD52 inhibitors (5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside [AICAR], (−)‐epigallocatechin [EGC]) or a RAD52‐phenylalanine 79 aptamer significantly restrained the growth of RAD52‐upregulated RECQL4ΔC HCT116 cells in vitro and in mouse xenografts. Remarkably, compared to single‐agent cisplatin or EGC treatment, cisplatin followed by low‐concentration EGC had a significant suppressive effect on RECQL4ΔC HCT116 cell growth in vivo. Together, the regimens targeting the RAD52‐mediated SSA pathway after anticancer treatment may be applicable for cancer patients with RECQL4 gene mutations.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Human RECQL4 represses the RAD52‐mediated single‐strand annealing pathway after ionizing radiation or cisplatin treatment

Kohzaki

Ootsuyama

Sun

et al. 2019

Intl Journal of Cancer

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Genomic alterations and clinical outcomes in patients with dedifferentiated liposarcoma

Jagosky

Anderson²,

Symanowski

et al. 2022

Cancer Medicine

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Purpose Patients with unresectable dedifferentiated liposarcoma (DDLPS) have poor overall outcomes. Few genomic alterations have been identified with limited therapeutic options. Experimental Design Patients treated at Levine Cancer Institute with DDLPS were identified. Next generation sequencing (NGS), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) testing were performed on tumor tissue collected at diagnosis or recurrence/progression. Confirmation of genomic alterations was performed by orthologous methods and correlated with clinical outcomes. Univariate Cox regression was used to identify genomic alterations associated with clinical outcomes. Results Thirty‐eight DDLPS patients with adequate tissue for genomic profiling and clinical data were identified. Patient characteristics included: median age at diagnosis (66 years), race (84.2% Caucasian), and median follow‐up time for the entire cohort was 12.1 years with a range from approximately 3.5 months to 14.1 years. Genes involved in cell cycle regulation, including MDM2 (74%) CDK4 (65%), and CDKN2A (23%), were amplified along with WNT/Notch pathway markers: HMGA2, LGR5, MCL1, and CALR (19%–29%). While common gene mutations were identified, PDE4DIP and FOXO3 were also mutated in 47% and 34% of patients, respectively, neither of which have been previously reported. FOXO3 was associated with improved overall survival (OS) (HR 0.37; p = 0.043) along with MAML2 (HR 0.30; p = 0.040). Mutations that portended worse prognosis included RECQL4 (disease‐specific survival HR 4.67; p = 0.007), MN1 (OS HR = 3.38; p = 0.013), NOTCH1 (OS HR 2.28, p = 0.086), and CNTRL (OS HR 2.42; p = 0.090). Conclusions This is one of the largest retrospective reports analyzing genomic aberrations in relation to clinical outcomes for patients with DDLPS. Our results suggest therapies targeting abnormalities should be explored and confirmation of prognostic markers is needed. Dedifferentiated liposarcoma is one of the most common subtypes of soft tissue sarcoma yet little is known of its molecular aberrations and possible impact on outcomes. The work presented here is an evaluation of genetic abnormalities among a population of patients with dedifferentiated liposarcoma and how they corresponded with survival and risk of metastases. There were notable gene mutations and amplifications commonly found, some of which had interesting prognostic implications.

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Overexpression of MCM10 promotes cell proliferation and predicts poor prognosis in prostate cancer

Cui

Ning

et al. 2018

The Prostate

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BackgroundProstate cancer (PCa) is one of the most malignant tumors of the male urogenital system. There is an urgent need to identify novel biomarkers for PCa.MethodsIn this study, we evaluated the expression levels of MCM10 in prostate cancer by analyzing public datasets (including The Cancer Genome Atlas and GSE21032). Furthermore, loss of function assays was performed to evaluate the effects of MCM10 on cell proliferation, apoptosis, and colony formation. Furthermore, we performed microarray and bioinformatics analyses to explore the potential mechanisms of MCM10.ResultsIn the present study, we for the first time revealed MCM10 was significantly upregulated in PCa. Moreover, we found increased MCM10 expression was significantly associated with advanced clinical stage and high Gleason score PCa. Kaplan‐Meier analysis demonstrated higher MCM10 expression was associated with a poorer patient prognosis in PCa. Furthermore, loss of function assays showed that MCM10 knockdown inhibited cell proliferation and colony formation, but promoted cell apoptosis. Additionally, we performed microarray and bioinformatics analysis and found MCM10 regulated PCa progression by regulating a series of biological processes including cancer, cell death, and apoptosis.ConclusionsThese results suggest that MCM10 may be a potential diagnostic and therapeutic target for PCa.

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Human RecQL4 helicase plays multifaceted roles in the genomic stability of normal and cancer cells

Cited by 46 publications

References 80 publications

Human RECQL4 represses the RAD52‐mediated single‐strand annealing pathway after ionizing radiation or cisplatin treatment

Human RECQL4 represses the RAD52‐mediated single‐strand annealing pathway after ionizing radiation or cisplatin treatment

Genomic alterations and clinical outcomes in patients with dedifferentiated liposarcoma

Overexpression of MCM10 promotes cell proliferation and predicts poor prognosis in prostate cancer

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