The mechanism of cancer derived exosomal homeobox gene a-antisense transcript 3 regulating castration resistance of prostate cancer by sponging microRNA-29b-3p
Objective To investigate the role of exosomal long no-coding RNA(lncRNA)ho-meobox gene a-antisense transcript 3(HOXA-AS3)in castration resistance and progression of prostate cancer(PCa).Methods Construct a co-culture system between PC-3 and LNCaP.The dual luciferase re-porter gene detection,PCR(polymerase chain reaction)and Rescue were conducted to verify the role of ex-osomes in castration resistance and progression of PCa.Animal experiments and human prostate cancer tis-sue sections were conducted to investigate the role of HOXA-AS3 in the transition from androgen dependent prostate cancer(ADPC)to castration-resistant prostate cancer(CRPC).Two sample t-test or One-Way ANOVA was used for statistically analysis.Results The number of invasive cells in LNCaP containing ASO-NC group was significantly less than that in LNCaP containing miR-29b-3p-ASO group(116.00±5.10 vs.146.33±4.78,t=6.135,P＜0.05).The number of invasive cells in PC-3 containing mimic-NC group was significantly higher than that in PC-3 containing miR-29b-3p group(394.33±11.95 vs.111.67±7.41,t=28.425,P＜0.05).The content of HOXA-AS3 in LNCaP-HOXA-AS3-exo group is significantly higher than that in LNCaP-exo group(1.46±0.08 vs.1.01±0.02,t=7.634,P＜0.05).The content of HOXA-AS3 in PC-3-HOXA-AS3-ASO-exo group is significantly higher than that in PC-3-exo group(0.53±0.06 vs.1.00±0.09,t=5.943,P＜0.05).The overexpressed miR-29b-3p significantly reduced the luciferase intensity of HOXA-AS3-3'UTR wide type,STAT3-3'UTR wide type and Mcl-1-3'UTR wide type(1.00±0.04 vs.0.51±0.02,1.00±0.02 vs.0.56±0.04,1.00±0.02 vs.0.57±0.02,t=18.058,15.857,26.081,P＜0.01).The relative luciferase intensity of the group containing with pcDNA3.1-STAT3 and Mcl-1-promotor was significantly higher than that of the controlled group(1.72±0.05 vs.1.00±0.03,t=18.717,P＜0.05),and the expression of cytochrome c and caspase-9 was significantly less than that of the controlled group(0.81±0.01 vs.0.46±0.01,0.59±0.01 vs.0.28±0.01,t=92.492,97.212,P＜0.01).Conclusion HOXA-AS3 contributes to the castration resistance of PCa via sponging miR-29b-3p and regulating STAT3/Mcl-1/cytochrome c/caspase-9 axis.
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