期刊文献+

miRNA-98-5p靶向HMGA2调控结直肠癌细胞增殖、侵袭和上皮间质转化 被引量:7

miRNA-98-5p inhibits proliferation,invasion and EMT of colorectal cancer cells by targeting HMGA2
下载PDF
导出
摘要 目的:研究miRNA-98-5p在结直肠癌细胞中的表达水平及对癌细胞增殖和侵袭的影响,探讨miRNA-98-5p在结直肠癌中的临床意义及可能的分子机制。方法:收集2016年8月至2018年2月手术切除的结直肠癌组织标本60份,实时荧光定量PCR法检测结直肠癌组织和癌旁组织中miRNA-98-5p的表达水平,免疫组化检测分析HMGA2的表达强度。分析miRNA-98-5p与结直肠癌肿瘤生物学特征和HMGA2表达的相关性。实时荧光定量聚合酶链反应(qRT-PCR)检测miRNA-98-5p在结直肠癌细胞中的表达情况;应用miRNA-98-5p模拟物转染人结直肠癌HCT116细胞,CCK-8法检测细胞增殖情况,Transwell小室法检测细胞侵袭情况,Western blot检测HMGA2、E-cadherin和Vimentin蛋白表达。采用双荧光素酶活性实验验证miRNA-98-5p对HMGA2的靶向作用。构建裸鼠皮下移植瘤模型,观察肿瘤生长状况。结果:结直肠癌组织miRNA-98-5p的表达水平低于癌旁组织,结直肠癌组织HMGA2的表达水平高于癌旁组织(P<0.05)。相关性分析显示, HMGA2表达强度与miRNA-98-5p表达水平呈负相关(r=-0.536,P<0.001)。miRNA-98-5p在结直肠癌细胞中表达水平低于对应结直肠黏膜正常细胞(P<0.05);与转染阴性对照细胞比较,转染miRNA-98-5p模拟物的HCT116细胞增殖水平和侵袭能力均受到抑制(P<0.05),HMGA2、Vimentin蛋白表达水平降低,E-cadherin表达增高。双荧光素酶报告基因结果提示HMGA2是miRNA-98-5p的靶基因。裸鼠皮下成瘤实验结果显示与Blank组和NC组相比,实验组肿瘤生长缓慢,重量明显降低。结论:miRNA-98-5p在结直肠癌细胞中表达下调,且miRNA-98-5p通过调节HMGA2的表达从而影响结直肠癌细胞增殖、侵袭和上皮间质转化状态。 Objective: To investigate the role of miRNA-98-5 p on the proliferation and invasion of colorectal cancer cells and the possible regulatory mechanisms between miRNA-98-5 p and HMGA2. Methods: From August2016 to February 2018,60 surgical specimens were collected. There expression of miRNA-98-5 p and HMGA2 at mRNA level in colorectal cancer tissues and paracancerous tissues were quantified by quantitative real-time PCR.The correlation between miRNA-98-5 p and the biological features of colorectal cancer as well as HMGA2 expression was analyzed. The expression of miRNA-98-5 p in colorectal cancer was detected by real-time PCR. The miRNA-98-5 p was overexpressed by Lipofectamine 3000 transfection with miRNA-98-5 p mimics. The effects of miRNA-98-5 p on cell proliferation and invasion abilities were detected by CCK-8 assay and Transwell assay. The protein expression of high mobility group A2( HMGA2),E-cadherin and Vimentin was determined by Western blot.The regulatory mechanism between HMGA2 and miRNA-98-5 p in HCT116 cells was detected by dual-luciferase reporter assay. Subcutaneous tumor formation model in nude mice was used to evaluate the effects of miRNA-98-5 p on tumor growthin vivo. Results: The expression of miRNA-98-5 p was significantly decreased compared with adjacent tissues( P < 0. 05). The protein expression of HMGA2 was significantly increased compared with adjacent tissues. The HMGA2 and miRNA-98-5 p expression were negatively correlated( r =-0. 536,P < 0. 001). The results of CCK-8 assay and Transwell assay showed that overexpression of miRNA-98-5 p significantly reduced the proliferation and invasion abilities of colorectal cancer cells( P < 0. 05). Overexpression of miRNA-98-5 p decreased the protein level of HMGA2. Also,it upregulated the expression of E-cadherin and downregulated the expression of Vimentin. The result of dual-luciferase-3’ UTR reporter assay confirmed that miRNA-98-5 p bound to the3’ UTR of HMGA2. In vivo subcutaneous tumor formation experiment revealed that miRNA-98-5 p mimics inhibited the growth and volume of injected tumor. Conclusion:miRNA-98-5 p may suppress the colorectal cancer cell proliferation,invasion and epithelial-mesenchymal transition( EMT) by down-regulation of HMGA2.
作者 李红 邓文英 赵玉州 臧凯 李璐 罗素霞 Li Hong;Deng Wenying;Zhao Yuzhou;Zang Kai;Li Lu;Luo Suxia(Department of Internal Medicine,the Tumor Hospital Affiliated to Zhengzhou University(Henan Cancer Hospital),Henan Zhengzhou 450008,China)
出处 《现代肿瘤医学》 CAS 2019年第20期3565-3571,共7页 Journal of Modern Oncology
关键词 结直肠癌 微小RNA 细胞增殖和侵袭 上皮间质转化 高迁移率族蛋白2 colorectal cancer microRNA cell proliferation and invasion epithelial-mesenchymal transition(EMT) high mobility group A2
  • 相关文献

参考文献7

二级参考文献7

共引文献442

同被引文献71

引证文献7

二级引证文献8

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部