靶向SDHB基因的miR-142-5p调控结直肠癌细胞生长增殖与能量代谢的作用及机制研究

批准号:
81402010
项目类别:
青年科学基金项目
资助金额:
22.0 万元
负责人:
张德才
依托单位:
学科分类:
H1805.肿瘤表观遗传
结题年份:
2017
批准年份:
2014
项目状态:
已结题
项目参与者:
刘少俊、肖志明、陈雄、艾飞艳、任为国、张学梅、束鹏
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中文摘要
SDHB是肿瘤抑制基因。我们前期研究表明,SDHB在结直肠癌中表达下调,与癌细胞生长增殖、能量代谢及不良预后密切相关,是一个重要的结直肠癌相关基因,然而其在结直肠癌中表达下调及作用机制尚不清楚。最近,我们利用生物信息软件筛选出靶向调控SDHB的miRNA—miR-142-5p,且初步发现miR-142-5p可负向调控SDHB的表达。由此,我们推测:miR-142-5p在结直肠癌中靶向SDHB介导调控细胞生长增殖与能量代谢。本项目将结合生物信息学和分子生物学技术等,对作用于SDHB的miR-142-5p进行体内外的鉴定与功能研究,对miR-142-5p通过SDHB介导调控细胞生长增殖与能量代谢的作用及分子机制进行深入研究,为应用外源性miRNA抑制结直肠癌细胞生长增殖提供理论和实验依据。
英文摘要
SDHB is a tumor suppressor gene. Our previous studies have shown that SDHB was downregulated in colorectal cancer and was closely related to cancer cell growth and proliferation, energy metabolism and poor prognosis. Our results indicated that SDHB is an important tumor suppressor gene associated with colorectal cancer, however, the mechanisms by which disruption of SDHB leads to neoplasia are largely unknown. Recently, we predicted that miR-124-5p could target SDHB through binding to 3’UTR of SDHB mRNA by using bioinformatics software and found miR-124-5p could negatively regulate the expression of SDHB. Thus, we hypothesized that, miR-142-5p can regulate cell growth and proliferation and energy metabolism in colorectal cancer by targeting SDHB. This project was designed to identify miR-142-5p and investigate its biological functions in vitro and in vivo, and to study the mechanisms by which miR-142-5p regulates cell growth and proliferation and energy metabolism by targeting SDHB in colorectal cancer. This results will provide theoretical and experimental bases for inhibition of cell growth and proliferation of colorectal cancer by application of exogenous miRNA.
SDHB是肿瘤抑制基因。前期研究表明SDHB在结直肠癌中表达下调,与癌细胞生长增殖、能量代谢及不良预后密切相关,然而其在结直肠癌中表达下调及相关作用机制尚未阐明。生物信息学软件预测miR-142-5p可靶向SDHB基因。本研究首先在结直肠癌组织及癌旁无瘤组织中运用qPCR和原位杂交检测发现,miR-142-5p在癌组织中表达上调,与预后呈正相关;且与SDHB在结直肠癌组织中的表达呈负相关。而在人结直肠癌细胞模型中,miR-142-5p同样对SDHB具有负向调控作用,荧光素酶报告基因实验亦证实SDHB为miR-142-5p的靶基因。随后体内外实验均证实miR-142-5p通过靶向下调SDHB基因的表达而促进结直肠癌细胞的增殖、抑制结直肠癌细胞的凋亡,且体外实验证实miR-142-5p通过靶向下调SDHB基因的表达促进了结直肠癌细胞有氧糖酵解。本研究还发现,下调SDHB通过激活AMPK促进结直肠癌细胞增殖与侵袭,而SDHB对结直肠癌细胞有氧糖酵解的调节可能并非通过AMPK。综上所述,本研究证实miR-142-5p可通过靶向调控SDHB基因的表达而促进结直肠癌细胞的增殖、抑制结直肠癌细胞的凋亡以及促进结直肠癌细胞有氧糖酵解,且AMPK介导了SDHB在结直肠癌细胞增殖侵袭中的作用;该结果表明miR-142-5p可能为重要的结直肠癌预后标记物,并可能为生物治疗提供新靶点。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
SDHB downregulation facilitates the proliferation and invasion of colorectal cancer through AMPK functions excluding those involved in the modulation of aerobic glycolysis.
SDHB 下调通过 AMPK 功能(不包括参与有氧糖酵解调节的功能)促进结直肠癌的增殖和侵袭
DOI:10.3892/etm.2017.5482
发表时间:2018-01
期刊:Experimental and therapeutic medicine
影响因子:2.7
作者:Xiao Z;Liu S;Ai F;Chen X;Li X;Liu R;Ren W;Zhang X;Shu P;Zhang D
通讯作者:Zhang D
miR-142-5p promotes development of colorectal cancer through targeting SDHB and facilitating generation of aerobic glycolysis
miR-142-5p通过靶向SDHB并促进有氧糖酵解的产生促进结直肠癌的发展
DOI:10.1016/j.biopha.2017.05.134
发表时间:2017-08-01
期刊:BIOMEDICINE & PHARMACOTHERAPY
影响因子:7.5
作者:Liu, Shaojun;Xiao, Zhiming;Zhang, Decai
通讯作者:Zhang, Decai
国内基金
海外基金
