LncRNA AFAP1-AS1 exhibits oncogenic characteristics and promotes gemcitabine-resistance of cervical cancer cells through miR-7-5p/EGFR axis  

作　　者：CHAOQUN WANG TING ZHANG CHAOHE ZHANG 

机构地区：[1]Department of Gynecology,Aviation General Hospital,Beijing,100020,China [2]Department of Burn and Skin Surgery,First Affiliated Hospital of Air Force Military Medical University,Xi’an,710032,China [3]Department of Oncology and Hematology,Second Hospital of Jilin University,Changchun,130000,China

出　　处：《Oncology Research》2024年第12期1867-1879,共13页肿瘤学研究（英文）

摘　　要：Background:Drug resistance is the main factor contributing to cancer recurrence and poor prognosis.Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy.In our study,the role of long non-coding RNA(lncRNA)AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells.Methods:Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method.The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis.The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay.Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium(MTT),soft agar,and colony formation experiments.Cell cycle and apoptosis were detected byflow cytometry.Results:Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis.Besides,patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group.AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells.In addition,AFAP1-AS1 mediated epidermal growth factor receptor(EGFR)expression by serving as a molecular sponge for microRNA-7a-5p(miR-7-5p).This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance.Conclusions:In general,the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer,providing potential targets for the management of cervical cancer.

关 键 词：Long non-coding RNA(lncRNA)AFAP1-AS1 miR-7-5p Epidermal growth factor receptor(EGFR) Gemcitabine-resistance Cervical cancer 

分 类 号：R737.33[医药卫生—肿瘤]