机构：[1]Center for Systems Biology, Soochow University, Suzhou 215006, China[2]School of Nanotechnology, Suzhou Industrial Park Institute of Services Outsourcing,Suzhou 215006, China[3]Institutes for Systems Genetics, West ChinaHospital, Sichuan University, Chengdu 610041, China
High-grade serous ovarian cancer (HGSC), the most common ovarian carcinoma type, is associated with the highest mortality rate among all gynecological malignancies. As chemoresistance has been demonstrated as the major challenge in improving the prognosis of HGSC patients, we here aimed to identify microRNA (miRNA) biomarkers for predicting platinum resistance and further explore their functions in HGSC.
We developed and applied our network vulnerability-based and knowledge-guided bioinformatics model first time for the study of drug-resistance in cancer. Four miRNA biomarkers (miR-454-3p, miR-98-5p, miR-183-5p and miR-22-3p) were identified with potential in stratifying platinum-sensitive and platinum-resistant HGSC patients and predicting prognostic outcome. Among them, miR-454-3p and miR-183-5p were newly discovered to be closely implicated in platinum resistance in HGSC. Functional analyses highlighted crucial roles of the four miRNA biomarkers in platinum resistance through mediating transcriptional regulation, cell proliferation and apoptosis. Moreover, expression patterns of the miRNA biomarkers were validated in both platinum-sensitive and platinum-resistant ovarian cancer cells.
With bioinformatics modeling and analysis, we identified and confirmed four novel putative miRNA biomarkers, miR-454-3p, miR-98-5p, miR-183-5p and miR-22-3p that could serve as indicators of resistance to platinum-based chemotherapy, thereby contributing to the improvement of chemotherapeutic efficiency and optimization of personalized treatments in HGSC.
基金：
National Natural Science Foundation of China
(Grant Nos. 31670851, 31600670 and 31900490), Jiangsu Planned Projects
for Postdoctoral Research Funds (2018K173C), China Postdoctoral Science
Foundation (2019M651938) and the Natural Science Foundation of the
Jiangsu Higher Education Institutions of China (Grant Nos. 18KJD520003 and
19KJB180027).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
无
最新[2023]版：
大类|1 区医学
小类|2 区医学：研究与实验2 区肿瘤学
第一作者：
第一作者机构：[1]Center for Systems Biology, Soochow University, Suzhou 215006, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Qi Xin,Yu Chunjiang,Wang Yi,et al.Network vulnerability-based and knowledge-guided identification of microRNA biomarkers indicating platinum resistance in high-grade serous ovarian cancer.[J].Clinical and translational medicine.2019,8(1):28.doi:10.1186/s40169-019-0245-6.
APA：
Qi Xin,Yu Chunjiang,Wang Yi,Lin Yuxin&Shen Bairong.(2019).Network vulnerability-based and knowledge-guided identification of microRNA biomarkers indicating platinum resistance in high-grade serous ovarian cancer..Clinical and translational medicine,8,(1)
MLA：
Qi Xin,et al."Network vulnerability-based and knowledge-guided identification of microRNA biomarkers indicating platinum resistance in high-grade serous ovarian cancer.".Clinical and translational medicine 8..1(2019):28
