Jing Long1, Jun-You Zhu1, Yong-Bin Liu2, Kun Fu1, Yan Tian1, Pei-Yao Li3, Wen-Qing Yang3, Si-Yu Yang3, Ji-Ye Yin4, Gang Yin5, Yu Zhang6. 1. Obstetrics and Gynecology Department, Xiangya Hospital, Central South University, China. 2. Institution of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, China. 3. Obstetrics and Gynecology Department, Xiangya Hospital, Central South University, China; Hunan Provincial Gynecological Cancer Diagnosis and Treatment Engineering Research Center, China. 4. Institution of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, China; Hunan Provincial Gynecological Cancer Diagnosis and Treatment Engineering Research Center, China. 5. Department of Pathology, School of Basic Medical Science, Central South University, China. 6. Obstetrics and Gynecology Department, Xiangya Hospital, Central South University, China; Hunan Provincial Gynecological Cancer Diagnosis and Treatment Engineering Research Center, China. Electronic address: cszhangyu@126.com.
Abstract
OBJECTIVE: To investigate the role of HELQ in chemo-resistance of epithelial ovarian carcinoma (EOC), which is a critical factor of patients' prognosis. METHODS: Immunohistochemistry, survival analysis of our 87 EOC patients and bioinformatics analysis of The Cancer Genome Atlas (TCGA) datasets (Nature, 2011) disclosed the clinical importance of HELQ expression. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western Blot analyses of EOC tissue were used to confirm it. Ectopic overexpression and RNA interference knockdown of HELQ were carried out in OVCAR3 and A2780 cell lines, respectively, to determine the effect of altered HELQ expression on cellular response to cisplatin by CCK8 assay. The DNA repair capacity of these cells was evaluated by using host-cell reactivation assay. Western Blot analyses were carried out to determine the effect of HLEQ on the DNA repair genes by using cells with altered HELQ expression. RESULTS: HELQ expression associates with response of EOC patients to platinum-based chemotherapy and their overall survival (OS), disease free survival (DFS). HELQ overexpression or knockdown, respectively, increased and decreased the cellular resistance to cisplatin, DNA repair activity, and expression of DNA repair proteins of Nucleotide excision repair (NER) pathway. CONCLUSIONS: HELQ plays an important role in regulating the expression of DNA repair proteins NER pathway which, in turn, contributes to cellular response to cisplatin and patients' response to platinum-based chemotherapy. Our results demonstrated that HELQ could serve as a novel indicator for chemo-resistance of EOC, which can predict the prognosis of the disease.
OBJECTIVE: To investigate the role of HELQ in chemo-resistance of epithelial ovarian carcinoma (EOC), which is a critical factor of patients' prognosis. METHODS: Immunohistochemistry, survival analysis of our 87 EOC patients and bioinformatics analysis of The Cancer Genome Atlas (TCGA) datasets (Nature, 2011) disclosed the clinical importance of HELQ expression. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western Blot analyses of EOC tissue were used to confirm it. Ectopic overexpression and RNA interference knockdown of HELQ were carried out in OVCAR3 and A2780 cell lines, respectively, to determine the effect of altered HELQ expression on cellular response to cisplatin by CCK8 assay. The DNA repair capacity of these cells was evaluated by using host-cell reactivation assay. Western Blot analyses were carried out to determine the effect of HLEQ on the DNA repair genes by using cells with altered HELQ expression. RESULTS:HELQ expression associates with response of EOC patients to platinum-based chemotherapy and their overall survival (OS), disease free survival (DFS). HELQ overexpression or knockdown, respectively, increased and decreased the cellular resistance to cisplatin, DNA repair activity, and expression of DNA repair proteins of Nucleotide excision repair (NER) pathway. CONCLUSIONS:HELQ plays an important role in regulating the expression of DNA repair proteins NER pathway which, in turn, contributes to cellular response to cisplatin and patients' response to platinum-based chemotherapy. Our results demonstrated that HELQ could serve as a novel indicator for chemo-resistance of EOC, which can predict the prognosis of the disease.
Authors: Tabitha Jenkins; Sarah J Northall; Denis Ptchelkine; Rebecca Lever; Andrew Cubbon; Hannah Betts; Vincenzo Taresco; Christopher D O Cooper; Peter J McHugh; Panos Soultanas; Edward L Bolt Journal: NAR Cancer Date: 2021-01-12