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
Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic targets.Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC ma...Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic targets.Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC malignant progression.It is well known that the long noncoding RNA AFAP1-AS1 plays a crucial role in various tumors,but whether AFAP1-AS1 is involved in the mitosis of TNBC cells remains unknown.In this study,we investigated the functional mechanism of AFAP1-AS1 in targeting Polo-like Kinase 1(PLK1)activation and participating in mitosis of TNBC cells.We detected the expression of AFAP1-AS1 in the TNBC patient cohort and primary cells by in situ hybridization(ISH),northern blot,fluorescent in situ hybridization(FISH)and cell nucleus/cytoplasm RNA fraction isolation.High AFAP1-AS1 expression was negatively correlated with overall survival(OS),disease-free survival(DFS),metastasis-free survival(MFS)and recurrence-free survival(RFS)in TNBC patients.We explored the function of AFAP1-AS1 by transwell,apoptosis,immunofluorescence(IF)and patient-derived xenograft(PDX)models in vitro and in vivo.We found that AFAP1-AS1 promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth,migration and invasion.Mechanistically,AFAP1-AS1 activated phosphorylation of the mitosis-associated kinase PLK1 protein.Elevated levels of AFAP1-AS1 in TNBC primary cells increased PLK1 pathway downstream gene expression,such as CDC25C,CDK1,BUB1 and TTK.More importantly,AFAP1-AS1 increased lung metastases in a mouse metastasis model.Taken together,AFAP1-AS1 functions as an oncogene that activates the PLK1 signaling pathway.AFAP1-AS1 could be used as a potential prognostic marker and therapeutic target for TNBC.展开更多
Objective This meta-analysis explored whether the expression of actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)is related to the prognosis and clinicopathological features of patients with cancer.Method...Objective This meta-analysis explored whether the expression of actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)is related to the prognosis and clinicopathological features of patients with cancer.Methods PubMed,EMBASE,and Cochrane Library were systematically searched.Hazard ratios(HRs)with 95%confidence intervals(CIs)were used to assess the prognostic value based on overall survival(OS),disease-free survival(DFS),and progression-free survival(PFS).Odds ratios(ORs)with 95%CIs were used to determine the relationships between AFAP1-AS1 and clinicopathological features,such as large tumor size(LTS),high tumor stage(HTS),poor histological grade(PHG),lymph node metastasis(LNM),and distant metastasis(DM).Results Thirty-five eligible articles and 3433 cases were analyzed.High AFAP1-AS1 expression,compared to low AFAP1-AS1 expression,correlated with significantly shorter OS(HR=2.15,95%CI=1.97-2.34,P<0.001),DFS(HR=1.37,95%CI=1.19-1.57,P<0.001),and PFS(HR=1.97,95%CI=1.56-2.50,P<0.001)in patients with cancer.In various cancers,elevated AFAP1-AS1 expression was significantly associated with LTS(OR=2.76,95%CI=2.16-3.53,P<0.001),HTS(OR=2.23,95%CI=1.83-2.71,P<0.001),and PHG(OR=1.39,95%CI=1.08-1.79,P=0.01)but not LNM(OR=1.59,95%CI=0.88-2.85,P=0.12)or DM(OR=1.81,95%CI=0.90-3.66,P=0.10).Conclusion High AFAP1-AS1 expression was associated with prognostic and clinicopathological features,suggesting that AFAP1-AS1 is a prognostic biomarker for human cancers.展开更多
目的:探讨血浆长链非编码RNA(long non-coding RNA,lncRNA)肌动蛋白纤维相关蛋白1-反义RNA1(actin filament-associated protein 1-antisense RNA1,AFAP1-AS1)和Y染色体性别决定基因簇2重叠转录本(sex-determining region of Y chromoso...目的:探讨血浆长链非编码RNA(long non-coding RNA,lncRNA)肌动蛋白纤维相关蛋白1-反义RNA1(actin filament-associated protein 1-antisense RNA1,AFAP1-AS1)和Y染色体性别决定基因簇2重叠转录本(sex-determining region of Y chromosome-box2 overlapping transcript,SOX2OT)表达水平对于非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床诊断价值。方法:留取48例NSCLC患者(NSCLC组)和48例良性肺病患者(对照组)血液标本,采用实时定量PCR检测lncRNA AFAP1-AS1和lncRNA SOX2OT相对表达水平,评价二者诊断NSCLC的可行性及效能,同时检测血清癌胚抗原水平。结果:NSCLC患者血浆lncRNA AFAP1-AS1和lncRNA SOX2OT表达水平显著高于对照组(t=6.236,5.680,P均<0.01),lncRNA AFAP1-AS1和lncRNA SOX2OT鉴别诊断NSCLC与良性肺病的受试者工作特征曲线下面积(AUC)分别为0.875(95%CI:0.804~0.947,P<0.05)和0.787(95%CI:0.691~0.883,P<0.05)。二者联合血清癌胚抗原可提高诊断的AUC。结论:NSCLC患者血浆中lncRNA AFAP1-AS1和lncRNA SOX2OT表达明显上调,二者联合血清癌胚抗原对NSCLC的诊断效能优于单独应用。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supported by the Natural Science Foundation of China(Nos.82002782,82202657)the Guangdong Basic and Applied Basic Research Foundation(2022A1515012021,2020A1515110930).
文摘Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic targets.Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC malignant progression.It is well known that the long noncoding RNA AFAP1-AS1 plays a crucial role in various tumors,but whether AFAP1-AS1 is involved in the mitosis of TNBC cells remains unknown.In this study,we investigated the functional mechanism of AFAP1-AS1 in targeting Polo-like Kinase 1(PLK1)activation and participating in mitosis of TNBC cells.We detected the expression of AFAP1-AS1 in the TNBC patient cohort and primary cells by in situ hybridization(ISH),northern blot,fluorescent in situ hybridization(FISH)and cell nucleus/cytoplasm RNA fraction isolation.High AFAP1-AS1 expression was negatively correlated with overall survival(OS),disease-free survival(DFS),metastasis-free survival(MFS)and recurrence-free survival(RFS)in TNBC patients.We explored the function of AFAP1-AS1 by transwell,apoptosis,immunofluorescence(IF)and patient-derived xenograft(PDX)models in vitro and in vivo.We found that AFAP1-AS1 promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth,migration and invasion.Mechanistically,AFAP1-AS1 activated phosphorylation of the mitosis-associated kinase PLK1 protein.Elevated levels of AFAP1-AS1 in TNBC primary cells increased PLK1 pathway downstream gene expression,such as CDC25C,CDK1,BUB1 and TTK.More importantly,AFAP1-AS1 increased lung metastases in a mouse metastasis model.Taken together,AFAP1-AS1 functions as an oncogene that activates the PLK1 signaling pathway.AFAP1-AS1 could be used as a potential prognostic marker and therapeutic target for TNBC.
基金Supported by a grant from the“Ten Thousand Plan”Youth Talent Project in Yunnan Province(no grant number is applicable).
文摘Objective This meta-analysis explored whether the expression of actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)is related to the prognosis and clinicopathological features of patients with cancer.Methods PubMed,EMBASE,and Cochrane Library were systematically searched.Hazard ratios(HRs)with 95%confidence intervals(CIs)were used to assess the prognostic value based on overall survival(OS),disease-free survival(DFS),and progression-free survival(PFS).Odds ratios(ORs)with 95%CIs were used to determine the relationships between AFAP1-AS1 and clinicopathological features,such as large tumor size(LTS),high tumor stage(HTS),poor histological grade(PHG),lymph node metastasis(LNM),and distant metastasis(DM).Results Thirty-five eligible articles and 3433 cases were analyzed.High AFAP1-AS1 expression,compared to low AFAP1-AS1 expression,correlated with significantly shorter OS(HR=2.15,95%CI=1.97-2.34,P<0.001),DFS(HR=1.37,95%CI=1.19-1.57,P<0.001),and PFS(HR=1.97,95%CI=1.56-2.50,P<0.001)in patients with cancer.In various cancers,elevated AFAP1-AS1 expression was significantly associated with LTS(OR=2.76,95%CI=2.16-3.53,P<0.001),HTS(OR=2.23,95%CI=1.83-2.71,P<0.001),and PHG(OR=1.39,95%CI=1.08-1.79,P=0.01)but not LNM(OR=1.59,95%CI=0.88-2.85,P=0.12)or DM(OR=1.81,95%CI=0.90-3.66,P=0.10).Conclusion High AFAP1-AS1 expression was associated with prognostic and clinicopathological features,suggesting that AFAP1-AS1 is a prognostic biomarker for human cancers.
