Experimental Study On MiR-23a-5p/TP53INP1 Regulating Gemcitabine Resistance In Pancreatic Cancer Cell

OBJECTIVE:Gemcitabine is the first-line drug in the treatment of pancreatic cancer,but its therapeutic effect is greatly limited by chemo therapy resistance.In recent years,non coding RNA plays a key role in the regμlation of chemosensitivity.This study explored the molecμlar mechanism of miRNA in regμlating gemcitabine resistance in pancreatic cancer.METHOD:The qPCR was used to detect the miR-23a-5p expres sion levels in clinical specimens of pancreatic cancer patients admitted from January2015 to December2018 in the Affiliated Hospital of Guilin Medical College.For cellμlar experiment,the effect of miR-23a-5p on the expression of tumor protein p53-inducible nuclear protein1（TP53INP1）and cell proliferation and apoptosis-related factors under gemcitabine treatment was studied.The CCK-8 assay was used to examine the cell proliferation,and flow cytometry was done to test cell apoptosis.The luciferase repor ter experiment was used to detect whether miR-23a-5p and TP53INP1 acted directly.The animal model of pancreatic cancer subcutaneous tumor for mation was constructed to detect the effect of miR-23a-5p on tumor size and gemcitabine resistance in animals.All experimental data were the aver age of three independent experiments.RESΜLT:The expression of miR-23a-5p in drug-resistant tissues increased significantly（2.267±0.334,t=4.355,P<0.01）,miR-23a-5p directly targeted and regμlated TP53INP1 to reduce its expression（0.423±0.095,t=5.649,P<0.01）,and the proliferation activity of pancreaticcancer cells over expressing miR-23a-5p was significantly increased(IC₅₀=13.230)as comp ared with the control group(IC₅₀=8.320,t=5.119,P<0.01).As compared with the control group[（30.710±0.566）%],the proportion of apoptosis was significantly decreased[（15.080±0.838）%,t=7.163,P<0.01].As compared with miR-23a-5p alone group(IC₅₀=12.570),the proliferation level of pancreaticcancer cells treated with TP53INP1 and miR-23a-5p was signific antly decreased(IC₅₀=7.950,t=7.932,P<0.01).As compared with miR-23a-5p alone group（15.680±1.358）,the apoptosis level was signifi-cantly increased（32.350±3.212,t=6.764,P<0.01）under miR-23a-5p treatment.In vivo experimentsshowed that knockdown of miR-23a-5p gemcitabine signific antly inhibited tumor growth[（169.090±25.889）cm³,t=4.351,P<0.01;（0.097±0.031）g,t=3.776,P<0.01].CONCLUSION:miR-23a-5p mediates TP53INP1 regμlation of pancreatic cancer cell apoptosis and gemcitabine resistance.miR-23a-5p may serve as a potential target for pancreatic cancer in the treatment of gemc itabine chemotherapy.