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 ...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.展开更多
Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bi...Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bivariate experiments,single-cell sequencing,ROC analysis of clinical samples,and humanized mouse models.Results:LncRNA DLX6-AS1 inhibited PTEN by adsorbing miR-26a,promoting hepatic stellate cell activation in a dose/time-dependent manner;the axis demonstrated excellent diagnostic performance(AUC>0.9),and its inhibitors effectively reversed fibrosis in vivo.Conclusion:This study provides new biomarkers and targeted therapeutic strategies for liver fibrosis.展开更多
文摘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.
基金Study on the Correlation between the Regulation of the miR-26a/PTEN Axis by lncRNA DLX6-AS1 and Post-Hepatitis Liver Fibrosis(Project No.:YKK22233)。
文摘Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bivariate experiments,single-cell sequencing,ROC analysis of clinical samples,and humanized mouse models.Results:LncRNA DLX6-AS1 inhibited PTEN by adsorbing miR-26a,promoting hepatic stellate cell activation in a dose/time-dependent manner;the axis demonstrated excellent diagnostic performance(AUC>0.9),and its inhibitors effectively reversed fibrosis in vivo.Conclusion:This study provides new biomarkers and targeted therapeutic strategies for liver fibrosis.
