Effect of lncRNA AC092718.4 on drug resistance of breast cancer in HER2 positive and its possible mechanism
Objective To investigate the effect of long non-coding RNA(lncRNA)AC092718.4 on drug resistance of breast cancer in human epidermal growth factor receptor 2(HER2)positive and its possible mechanism.Methods(1)Breast cancerous tissues from breast cancer patients with trastuzumab non-drug resistance and drug resistance in HER2 positive were obtained(setting as the non-drug resistance group or the drug resistance group),and their mRNA and protein expressions of lncRNA AC092718.4,miR-135a-5p,and S100 calcium binding protein P(S100P)were detected.(2)Regarding HER2-positive breast cancerous cell line MDA-MB-361 cells,which were insensitive to trastuzumab,as primary drug resistant cell model,and regarding breast cancerous cell strain BT-474 cells as parent,the cell model of secondary drug resistance on trastuzumab(BT-474/TRA cells)was established.The expressions of lncRNA AC092718.4,miR-135a-5p,and S100P mRNA and protein of the three categories of cells were detected.After 48-hour intervention of trastuzumab in the same concentration,activity of the three categories of cells was detected.(3)MDA-MB-361 cells were obtained and assigned to sh-AC092718.4 group,sh-NC group,or control group for experiment,therein cells in the sh-AC092718.4 group and the sh-NC group were transfected with sh-AC092718.4 and sh-NC,respectively,whereas cells in the control group did not receive treatment.After 48-hour intervention of trastuzumab in the same concentration,activity of cells in the three groups were detected.(4)The starBase and TargetScan were used to predict potential targets of lncRNA AC092718.4 and miR-135a-5p,respectively.The dual luciferase reporter gene experiment was used to validate the targeted binding between lncRNA AC092718.4 and miR-135a-5p,and between miR-135a-5p and S100P.Results(1)Compared with the non-drug resistance group,the drug resistance group exhibited elevated expressions of lncRNA AC092718.4,S100P mRNA,and S100P protein,while a decreased expression of miR-135a-5p(P<0.05).(2)Compared with BT-474 cells,expressions of lncRNA AC092718.4,S100P mRNA,and S100P protein of BT-474/TRA cells and MDA-MB-361 cells were elevated,while miR-135a-5p expression was decreased,as well as cell activity of trastuzumab was greater after 48 hours of intervention(P<0.05).(3)Compared with the control group and the sh-NC group,the sh-AC092718.4 group yielded decreased activity of MDA-MB-361 cells(P<0.05).(4)The results of starBase prediction revealed that lncRNA AC092718.4 had targeted binding loci with miR-135a-5p;moreover,the results of TargetScan prediction indicated that there were targeted binding loci between miR-135a-5p and S100P.The results of dual luciferace reporter gene experiment interpreted that lncRNA AC092718.4 might bind directly to miR-135a-5p,and S100P was the target gene of miR-135a-5p.Conclusion Breast cancerous cells developing drug resistance on trastuzumab can be promoted by lncRNA AC092718.4.Down-regulating lncRNA AC092718.4 expression may relieve MDA-MB-361 cells on drug resistance of trastuzumab,and its mechanism may be involved lncRNA AC092718.4 as a competitive endogenous RNA competitively binding miR-135a-5p,thereby up-regulating S100P expression.
Breast cancerHuman epidermal growth factor receptor 2 positiveLong non-coding RNA AC092718.4Drug resistanceTrastuzumabMicroRNA-135a-5pS100 calcium binding protein P
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维普
