Helicase POLQ-like (HELQ) as a novel indicator of platinum-based chemoresistance for epithelial ovarian cancer

Long, Jing; Zhu, Junyou; Liu, Yongbin; Fu, Kun; Tian, Ye; Li, Peiyao; Yang, Wenqing; Yang, Siyu; Yin, Ji‐Ye; Yin, Gang; Zhang, Yu

doi:10.1016/j.ygyno.2018.03.006

Cited by 13 publications

(17 citation statements)

References 39 publications

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“…Epithelial ovarian cancer (EOC) was the most prevalent gynecologic malignancies worldwide . As ovarian tumors at the early stage have no specific symptoms, most of EOC patients are diagnosed at advanced phase of disease, and the overall five‐year survival rate is relatively low .…”

Section: Introductionmentioning

confidence: 99%

Cryptotanshinone suppresses cell proliferation and glucose metabolism via STAT3/SIRT3 signaling pathway in ovarian cancer cells

et al. 2018

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Ovarian cancer is the most malignant gynecologic cancer among women worldwide. Cryptotanshinone (CT), isolated from Salvia miltiorrhiza Bunge, has been identified as a potential therapeutic agent in treating several malignant tumors, but the molecular mechanism of CT in ovarian cancer still remains illustrated. Here, we sought to elucidate the regulatory function of CT on cell glucose metabolism in ovarian cancer. The treatment of CT on ovarian cancer cells effectively inhibited glucose uptake and lactate production in ovarian cancer cells. The expression levels of glycolysis‐related proteins, such as GLUT1, LDHA, and HK2, were decreased by the treatment of CT detected by qRT‐PCR and immunoblotting. Mechanistically, CT exerted its anti‐tumor effect by targeting STAT3/SIRT3/HIF‐1α signaling pathway in vitro and in vivo, which could be rescued by the introduction of SIRT3 shRNA in ovarian cancer cells. The clinical data showed that the expression level of STAT3 in ovarian cancer patients’ sera and tissues was positively correlated with those of GLUT1, LDHA, HK2 and HIF‐1α, but negatively with that of SIRT3These findings provide evidence that CT inhibited cellular glycolysis‐induced cell growth and proliferation through repression of STAT3/SIRT3/HIF‐1α signaling pathway, indicating that CT may be developed as a chemotherapeutic agent to treat ovarian cancer.

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Section: Introductionmentioning

confidence: 99%

Cryptotanshinone suppresses cell proliferation and glucose metabolism via STAT3/SIRT3 signaling pathway in ovarian cancer cells

et al. 2018

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“…To our best knowledge, HELQ/EGR3/ZNF667/ SOWAHC were not described to be relevant with CLL previously. As an important regulation factor of DNA repair pathway, HELQ (Helicase POLQ-like protein) expression is demonstrated as an indicator of resistance to platinum based chemotherapy in epithelial ovarian cancer [28]. Hui Cheng et al demonstrate that EGR3 (Early growth response protein 3) is a strong limiting factor for potential of hematopoietic stem cell proliferation [29].…”

Section: Resultsmentioning

confidence: 99%

HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia

Guo

Gao

et al. 2021

J Transl Med

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Background IGHV mutation status is a crucial prognostic biomarker for CLL. In the present study, we investigated the transcriptomic signatures associating with IGHV mutation status and CLL prognosis. Methods The co-expression modules and hub genes correlating with IGHV status, were identified using the GSE28654, by ‘WGCNA’ package and R software (version 4.0.2). The over-representation analysis was performed to reveal enriched cell pathways for genes of correlating modules. Then 9 external cohorts were used to validate the correlation of hub genes expression with IGHV status or clinical features (treatment response, transformation to Richter syndrome, etc.). Moreover, to elucidate the significance of hub genes on disease course and prognosis of CLL patients, the Kaplan–Meier analysis for the OS and TTFT of were performed between subgroups dichotomized by the median expression value of individual hub genes. Results 2 co-expression modules and 9 hub genes ((FCRL1/FCRL2/HELQ/EGR3LPL/LDOC1/ZNF667/SOWAHC/SEPTIN10) correlating with IGHV status were identified by WGCNA, and validated by external datasets. The modules were found to be enriched in NF-kappaB, HIF-1 and other important pathways, involving cell proliferation and apoptosis. The expression of hub genes was revealed to be significantly different, not only between CLL and normal B cell, but also between various types of lymphoid neoplasms. HELQ expression was found to be related with response of immunochemotherapy treatment significantly (p = 0.0413), while HELQ and ZNF667 were expressed differently between stable CLL and Richter syndrome patients (p < 0.0001 and p = 0.0278, respectively). By survival analysis of subgroups, EGR3 expression was indicated to be significantly associated with TTFT by 2 independent cohorts (GSE39671, p = 0.0311; GSE22762, p = 0.0135). While the expression of HELQ and EGR3 was found to be associated with OS (p = 0.0291 and 0.0114 respectively).The Kras, Hedgehog and IL6-JAK-STAT3 pathways were found to be associating with the expression of hub genes, resulting from GSEA. Conclusions The expression of HELQ and EGR3 were correlated with IGHV mutation status in CLL patients. Additionally, the expression of HELQ/EGR3 were prognostic markers for CLL associating with targetable cell signaling pathways.

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“…HELQ (Helicase POLQ-like), an ATP-dependent 3′-5′ DNA helicase, plays pivotal roles in DNA processing, including homologous recombination repair (Han et al, 2016). It has been reported to serve as an indicator of platinum-based chemoresistance for ovarian cancer (Long et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Identification of a DNA Repair Gene Signature and Establishment of a Prognostic Nomogram Predicting Biochemical-Recurrence-Free Survival of Prostate Cancer

Long

Ouyang

Zhang

et al. 2021

Front. Mol. Biosci.

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Background: The incidence of prostate cancer (PCa) is high and increasing worldwide. The prognosis of PCa is relatively good, but it is important to identify the patients with a high risk of biochemical recurrence (BCR) so that additional treatment could be applied.Method: Level 3 mRNA expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) to serve as training data. The GSE84042 dataset was used as a validation set. Univariate Cox, lasso Cox, and stepwise multivariate Cox regression were applied to identify a DNA repair gene (DRG) signature. The performance of the DRG signature was assessed based on Kaplan–Meier curve, receiver operating characteristic (ROC), and Harrell’s concordance index (C-index). Furtherly, a prognostic nomogram was established and evaluated likewise.Results: A novel four DRG signature was established to predict BCR of PCa, which included POLM, NUDT15, AEN, and HELQ. The ROC and C index presented good performance in both training dataset and validation dataset. The patients were stratified by the signature into high- and low-risk groups with distinct BCR survival. Multivariate Cox analysis revealed that the DRG signature is an independent prognostic factor for PCa. Also, the DRG signature high-risk was related to a higher homologous recombination deficiency (HRD) score. The nomogram, incorporating the DRG signature and clinicopathological parameters, was able to predict the BCR with high efficiency and showed superior performance compared to models that consisted of only clinicopathological parameters.Conclusion: Our study identified a DRG signature and established a prognostic nomogram, which were reliable in predicting the BCR of PCa. This model could help with individualized treatment and medical decision making.

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Helicase POLQ-like (HELQ) as a novel indicator of platinum-based chemoresistance for epithelial ovarian cancer

Cited by 13 publications

References 39 publications

Cryptotanshinone suppresses cell proliferation and glucose metabolism via STAT3/SIRT3 signaling pathway in ovarian cancer cells

Cryptotanshinone suppresses cell proliferation and glucose metabolism via STAT3/SIRT3 signaling pathway in ovarian cancer cells

HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia

Identification of a DNA Repair Gene Signature and Establishment of a Prognostic Nomogram Predicting Biochemical-Recurrence-Free Survival of Prostate Cancer

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