中国肿瘤生物治疗杂志2017，Vol.24Issue(6)：581-587,7.DOI:10.3872/j.issn.1007-385X.2017.06.002
MiR-142-5p通过靶向IGF2BP3调控多柔比星诱导的肝癌细胞凋亡
MiR-142-5p promotes hepatocellular carcinoma cell apoptosis induced by dexorubicin with targetting IGF2BP3
摘要
Abstract
Objective:To investigate the function and molecular mechanisms of micro RNA-142-5p (miR-142-5p) on the doxorubicin induced apoptosis of primary hepatocellular carcinoma (HCC).Methods:Paired HCC tissues and adjacent non-cancerous tissue specimens (2-5cm away from the lesion) were surgically collected from 88 patients who were diagnosed with primary HCC in Tumor Hospital Affiliated to Guangxi Medical University between October 2001 and July 2005.qRT-PCR was used to detect the miR-142-5p expressions in those HCC tissues,adjacent non-cancerous tissues,normal hepatocellular cell line and HCC cell lines.HCC SMMC-7721 cells were transfected with miR-142-5p mimics,and flow cytometry was used to determine the changes in doxorubicin (1 μg/ml) induced apoptosis of SMMC-7721 cells.Bioinformatics predicted that miR-142-5p could bind with insulin-like growth factor 2 Mrna-binding protein 3 (IGF2BP3),which was then validated by luciferase reporter gene assay.qRT-PCR and Western blotting were separately used to detect the mRNA and protein expressions of IGF2BP3 in SMMC-7721 cells that over-express miR-142-5p.Results:Compared with the adjacent non-tumor tissues,miR-142-5p was significantly lower in HCC tissues (-6.91 ± 2.61vs-11.59 ±2.59,P ＜0.01) and this decrease was also found in HCC cell line compared with normal human liver cells (P ＜ 0.01);over-expression of miR-142-5p significantly promoted the doxorubicin induced apoptosis of HCC SMMC-7721 cells ([49.4 ± 3.47] ％ vs [19.50 ± 1.74] ％,P ＜ 0.01).miR-142-5p over-expression could obviously inhibit the mRNA and protein expressions of IGF2BP3 in SMMC-7721 cells.Luciferase reporter gene assay also showed that miR-142-5p over-expression could inhibit the luciferase activity of 3'UTR of IGF2BP3.Conclusion:miR-142-5p expression significantly decreased in both HCC tissues and HCC cell lines.miR-142-Sp mimics transfection promoted doxorubicin induced apoptosis of HCC cells,and the mechanism probably related with miR-142-Sp targetting IGF2BP3 and further promote the apoptosis of HCC cells.关键词
肝细胞癌/miR-142-5p/多柔比星/凋亡/胰岛素样生长因子2 mRNA结合蛋白3基因Key words
hepatocellular carcinoma (HCC)/miR-142-5p/doxorubicin/apoptosis/insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) gene分类
医药卫生引用本文复制引用
胡烨,许小青,王冰晶,徐贺楠,侯晋,罗晓玲,梁安民,曹雪涛..MiR-142-5p通过靶向IGF2BP3调控多柔比星诱导的肝癌细胞凋亡[J].中国肿瘤生物治疗杂志,2017,24(6):581-587,7.基金项目
国家自然科学基金资助项目(No.31390431) （No.31390431）
国家重点基础研究发展规划(973计划)资助项目(No.2013CB530503).Project supported by the National Natural Science Foundation of China (No.31390431),and the National Key Basic Research and devepment Program (973) of China(No.2013CB530503) （973计划）
