>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息：
微小RNA-215-5p靶向eIF2a负向调控结肠癌细胞增殖
作者：秦宝山  郭云霞  韩莉 
单位：郑州人民医院 消化内科, 河南 郑州 450000
关键词：结肠癌 微小RNA-215-5p 真核细胞翻译起始因子2a 细胞增殖 
分类号：R735.35
出版年·卷·期（页码）：2020·39·第六期（780-787）
摘要：

目的：探讨微小RNA-215-5p（miR-215-5p）与真核细胞翻译起始因子2a（eIF2a）的靶向关系，分析其通路对结肠癌细胞增殖的调节作用。方法：选择结肠癌患者手术切除标本55例，以肿瘤组织作为观察组，以癌旁正常结肠黏膜组织作为对照组。应用实时荧光定量PCR法（qPCR）检测miR-215-5p的表达，应用免疫组化法检测结肠癌中eIF2a和Ki67的表达。选择结肠癌SW480细胞系，构建空白对照组、空载体转染组、miR-215-5p转染组、miR-215-5p和eIF2a共转染组，应用蛋白印迹法检测各组中eIF2a和Ki67的表达。应用双荧光素酶报告基因实验观察miR-215-5p与eIF2a的结合情况。结果：观察组miR-215-5p的表达明显低于对照组，miR-215-5p表达与肿瘤最大径大小及浸润深度相关；生存分析显示miR-215-5p与预后有关，MiR-215-5p均与eIF2a、Ki67呈负相关性，双荧光素酶报告基因实验显示miR-215-5p与eIF2a具有靶向关系。与空白对照组和空载体转染组比较，miR-215-5p转染组中eIF2a和Ki67的表达下降，共转染组能逆转上述改变。结论：miR-215-5p靶向eIF2a负向调控结肠癌细胞的增殖，miR-215-5p低表达与肿瘤形成及进展密切相关，检测miR-215-5p表达可能对结肠癌预后有提示意义。

Objective: To investigate the targeting relationship between microRNA-215-5p(miR-215-5p) and the eukaryotic translation initiation factor 2a(eIF2a), and to analyze the regulating effect on the proliferation of colon cancer cells. Methods: Tumor tissue from a total of 55 patients with colon cancer were taken as experimental group, and normal colonic mucosa were taken as a control group. Expressions of miR-215-5p were assessed by real time fluorescent quantitative PCR(qPCR), and expressions of eIF2a and Ki67 were assessed by immunohistochemical methods. Colon carcinoma cell lines SW480 was used to construct a blank control group, an empty vector transfection group, a miR-215-5p transfection group, a miR-215-5p, and a eIF2a co-transfection group. Expressions of eIF2a and Ki67 were assessed by Western blotting. The double luciferase reporter gene experiment was used to monitor the binding between miR-215-5p and eIF2a. Results: The expression of miR-215-5p was significantly lower in the colon cancer group than that in the control group. The expression of miR-215-5p was significantly correlated with the maximum diameter and depth of invasion. MiR-215-5p was found to be correlated with prognosis:negative correlation was found between miR-215-5p and eIF2a, miR-215-5p and Ki67. A targeting relationship was found between miR-215-5p and eIF2a by the double luciferase reporter gene experiment. The expressions of Ki67 and eIF2a were lower in miR-215-5p transfected group compared to those in the blank control group and the empty vector transfected group. Such changes could be reversed in the co-transfection group. Conclusion: miRNA-215-5p negatively regulates eIF2a expression and inhibits colon cancer cell proliferation. Low expression levels of miR-215-5p are closely related to the formation and progression of colon cancer. Measurements of miR-215-5p expression may be helpful for clinical prognosis.
参考文献：

[1] MA Y L,WANG C Y,GUAN Y J,et al.Long noncoding RNA ROR promotes proliferation and invasion of colorectal cancer by inhibiting tumor suppressor gene NF2 through interacting with miR-223-3p[J].Eur Rev Med Pharmacol Sci,2020,24(5):2401-2411.
[2] EKATERINA C,NATALIA B,PETER K.Kinases of eIF2a switch translation of mRNA subset during neuronal plasticity[J].Int J Mol Sci,2017,18(10):2213-2239.
[3] KOROMILAS A E.Roles of the translation initiation factor eIF2α serine 51 phosphorylation in cancer formation and treatment[J].Biochim Biophys Acta,2015,1849(7):871-880.
[4] LIU J,KE F,CHEN T,et al.MicroRNAs that regulate PTEN as potential biomarkers in colorectal cancer:a systematic review[J].J Cancer Res Clin Oncol,2020,146(4):809-820.
[5] MONTERDE-CRUZ L,RAMIREZ-SALAZAR E G,RICO-MARTINEZ G,et al.Circulating miR-215-5p and miR-642a-5p as potential biomarker for diagnosis of osteosarcoma in Mexican population[J].Hum Cell,2018,31(4):292-299.
[6] 蒋林哲,王月华,王立波,等.实时荧光定量PCR检测结肠癌中HER-2和TOPOⅡα mRNA的表达[J].现代医学,2020,48(1):26-30.
[7] LI Y,CHEN Z.The oncogenic role of microRNA-500a in colorectal cancer[J].Oncol Lett,2020,19(3):1799-1805.
[8] VYCHYTILOVA-FALTEJSKOVA P,MERHAUTOVA J,MACHACKOVA T,et al.MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9[J].Oncogenesis,2017,6(11):399-400.
[9] LIU S,ZHANG Y,HUANG C,et al.miR-215-5p is an anticancer gene in multiple myeloma by targeting RUNX1 and deactivating the PI3K/AKT/mTOR pathway[J].J Cell Biochem,2020,121(2):1475-1490.
[10] ROZPEDEK W,PYTEL D,MUCHA B,et al.The role of the PERK/eIF2α/ATF4/CHOP signaling pathway in tumor progression during endoplasmic reticulum stress[J].Curr Mol Med,2016,16(6):533-544.
[11] TANAKA I,SATO M,KATO T,et al.eIF2β,a subunit of translation-initiation factor EIF2,is a potential therapeutic target for non-small cell lung cancer[J].Cancer Sci,2018,109(6):1843-1852.
[12] KIM J Y,HEO S H,SONG I H,et al.Activation of the PERK-eIF2α pathway is associated with tumor-infiltrating lymphocytes in HER2-positive breast cancer[J].Anticancer Res,2016,36(6):2705-2711.
[13] BURWICK N,AKTAS B H.The eIF2-alpha kinase HRI:a potential target beyond the red blood cell[J].Expert Opin Ther Targets,2017,21(12):1171-1177.
[14] REN W,LI Y,XIA X,et al.Arginine inhibits the malignant transformation induced by interferon-gamma through the NF-κB-GCN2/eIF2α signaling pathway in mammary epithelial cells in vitro and in vivo[J].Exper Cell Res,2018,15(7):236-247.
[15] BRUNELLI C,AMICI C,ANGELINI M,et al.The non-steroidal anti-inflammatory drug indomethacin activates the eIF2α kinase PKR,causing a translational block in human colorectal cancer cells[J].Biochem J,2012,443(2):379-386.
[16] SINGH A,BHATTACHARYYA N,SRIVASTAVA A,et al.MicroRNA-215-5p treatment suppresses mesothelioma progression via the MDM2-p53-signaling axis[J].Mol Ther,2019,27(9):1665-1680.
[17] CAI J,YANG J,LIU Q,et al.Selenium deficiency inhibits myocardial development and differentiation by targeting the mir-215-5p/CTCF axis in chicken[J].Metallomics,2019, 11(2):415-428.
[18] GAO J B,ZHU M N,ZHU X L.miRNA-215-5p suppresses the aggressiveness of breast cancer cells by targeting Sox9[J].FEBS Open Bio,2019,9(11):1957-1967.
[19] WANG S F,CHEN M S,CHOU Y C,et al.Mitochondrial dysfunction enhances cisplatin resistance in human gastric cancer cells via the ROS-activated GCN2-eIF2α-ATF4-xCT pathway[J].Oncotarget,2016,7(45):74132-74151.
[20] PODSZYWALOW-BARTNICKA P,CMOCH A,WOLCZYK M,et al.Increased phosphorylation of eIF2α in chronic myeloid leukemia cells stimulates secretion of matrix modifying enzymes[J].Oncotarget,2016,7(48):79706-79721.
[21] JU S M,JO Y S,JEON Y M,et al.Phosphorylation of eIF2α suppresses cisplatin-induced p53 activation and apoptosis by attenuating oxidative stress via ATF4-mediated HO-1 expression in human renal proximal tubular cells[J].Int J Mol Med,2017,40(6):1957-1964.
服务与反馈：
【文章下载】【发表评论】【查看评论】【加入收藏】
提示：您还未登录，请登录！点此登录
您是第 414655 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话：025-83272481 83272483
电子邮件： bjb@pub.seu.edu.cn

苏ICP备09058364