miR-362靶向Six1抑制宫颈癌细胞增殖、迁移的作用机制研究

doi:10.11904/j.issn.1002-3070.2019.04.005

摘要/Abstract

摘要： 目的探讨miR-362靶向Six1抑制宫颈癌细胞增殖、迁移的作用机制。方法选取本院宫颈癌患者142例,测定宫颈癌组织及癌旁组织中miR-362的表达水平;同时设Hela癌细胞组、miR-362mimics组、miR-362inhibitor组,测定各组癌细胞活力、癌细胞单克隆形成数目、癌细胞凋亡率、细胞周期、穿膜孔数以及Hela宫颈癌液miR-362、Six1 mRNA水平。结果宫颈癌组织中miR-362 mRNA表达水平低于癌旁组织(P＜0.05)。有淋巴血管间隙浸润、病理学分期越高、TNM分期越高、有淋巴结转移、浸润深度越深,miR-362mRNA表达率越低(P＜0.05)。miR-362mimics组OD值、存活率水平低于Hela癌细胞组(P＜0.05),miR-362inhibitor组OD值、存活率水平高于Hela癌细胞组、miR-362mimics组(P＜0.05)。miR-362mimics组克隆形成数目低于Hela癌细胞组(P＜0.05),miR-362inhibitor组克隆形成数目高于Hela癌细胞组、miR-362 mimics组(P＜0.05)。miR-362mimics组细胞凋亡率高于Hela癌细胞组(P＜0.05),miR-362 inhibitor组细胞凋亡率低于Hela癌细胞组、miR-362mimics组(P＜0.05)。miR-362mimics组G₁期高于Hela癌细胞组(P＜0.05),miR-362inhibitor组G₁期低于Hela癌细胞组、miR-362 mimics组(P＜0.05)。miR-362 mimics组细胞穿膜数低于Hela癌细胞组(P＜0.05),miR-362 inhibitor组穿膜数高于Hela癌细胞组、miR-362mimics组(P＜0.05)。miR-362 mimics组miR-362 mRNA表达水平高于Hela癌细胞组(P＜0.05),miR-362 inhibitor组miR-362 mRNA表达水平低于Hela癌细胞组、miR-362mimics组(P＜0.05)。miR-362 mimics组Six1 mRNA表达水平低于Hela癌细胞组(P＜0.05),miR-362inhibitor组Six1 mRNA表达水平高于Hela癌细胞组、miR-362mimics组(P＜0.05)。结论 miR-362在宫颈癌的发生和发展过程中发挥了肿瘤抑制作用;其机制与miR-362通过负调节Six1抑制癌细胞增殖、迁移和侵袭有关。

关键词: 微小RNA-362, Six1, 宫颈癌细胞, 增殖

Abstract: Objective To investigate the mechanism of Mi-362 targeting Six1 inhibiting proliferation and migration of cervical cancer cells.Methods The expression levels of microRNA-362 in cervical cancer tissues and adjacent tissues were measured in 142 patients with cervical cancer in our hospital.At the same time,Hela cancer cell group,microRNA-362 mimics group and microRNA-362 inhibitor group were set up to determine the viability of cancer cells,the number of monoclonal formation of cancer cells,the apoptotic rate of cancer cells,cell cycle,the number of perforations,and the levels of microRNA-362 and Six1 in cervical cancer fluid of Hela.Results The expression level of miR-362 in cervical cancer tissue was lower than that in adjacent tissue(P＜0.05).The higher the infiltration of lymphatic vessel space,pathological stage,TNM stage,lymph node metastasis and depth of infiltration,the lower the expression rate of miR-362(P＜0.05).The OD value and survival rate in the miR-362 mimics group were lower than those in the Hela cancer cells group(P＜0.05),while the OD value and survival rate in the mir-362 inhibitor group were higher than those in the Hela cancer cells group and the miR-362 mimics group(P＜0.05).The number of clones formed in the miR-362 mimics group was lower than that in the Hela cancer cell group(P＜0.05),and the number of clones formed in the miR-362 inhibitor group was higher than that in the Hela cancer cell group and the miR-362 mimimics group(P＜0.05).The apoptotic rate of miR-362 mimics group was higher than that of Hela cancer cell group(P＜0.05),and that of miR-362 inhibitor group was lower than that of Hela cancer cell group and miR-362 mimics group(P＜0.05).The G1 phase in the miR-362 mimics group was higher than that in the Hela cancer cell group(P＜0.05),and the G1 phase in the miR-362 inhibitor group was lower than that in the Hela cancer cell group and the miR-362 mimimics group(P＜0.05).The number of cell membrane penetration in the miR-362 mimics group was lower than that in the Hela cancer group(P ＜ 0.05),and that in the miR-362 inhibitor group was higher than that in the Hela cancer group and the miR-362 mimimics group(P＜0.05).The expression level of miR-362 in the miR-362 mimics group was higher than that in the Hela cancer cell group(P＜0.05),and the expression level of miR-362 in the miR-362 inhibitor group was lower than that in the Hela cancer cell group and the miR-362 mimics group(P＜0.05).The expression level of Six1 in the miR-362 mimics group was lower than that in the Hela cancer cell group(P＜0.05),and that in the miR-362 inhibitor group was higher than that in the Hela cancer cell group and the miR-362 mimics group(P＜0.05).Conclusion miR-362 plays an important inhibition in the occurrence and development of cervical cancer,and its mechanism is related to the inhibition of proliferation,migration and invasion of cancer cells by microRNA-362 through negative regulation of Six1.

Key words: MicroRNA-362, Six1, Cervical cancer cells, Proliferation

中图分类号:

R737.33

李景, 吴华珍, 刘继琐. miR-362靶向Six1抑制宫颈癌细胞增殖、迁移的作用机制研究[J]. 实用肿瘤学杂志, 2019, 33(4): 310-316.

LI Jing, WU Huazhen, LIU Jisuo. A study on the mechanism of mi-362 targeting six1 inhibiting proliferation and migration of cervical cancer cells[J]. Journal of Practical Oncology, 2019, 33(4): 310-316.

参考文献

1 Jeronimo J,Castle PE,Temin S,et al.Secondary prevention of cervical cancer:asco resource-stratified clinical practice guideline[J].J Glob Oncol,2016,3(5):635-657.
2 曲亚兰,谢宝芳,李丹阳.流式细胞术联合阴道镜活检在宫颈癌和癌前病变筛查中的意义[J].实用肿瘤学杂志,2017,31(1):31-34.
3 Sun L,Jiang R,Li J,et al.micoRNA-425-5p is a potential prognostic biomarker for cervical cancer[J].Ann Clin Biochem,2017,54(1):127-133.
4 Arrossi S,Temin S,Garland S,et al.primary prevention of cervical cancer:american society of clinical oncology resource-stratified guideline[J].J Oncol Pract,2017,13(7):452-457.
5 Veluchamy JP,Heeren AM,Spanholtz J,et al.high-efficiency lysis of cervical cancer by allogeneic NK cells derived from umbilical cord progenitors is independent of hla status[J].Cancer Immunol Immunother,2017,66(1):51-61.
6 Li JQ,Rong ZH,Chen X,et al.mcmda:matrix completion for mirna-disease association prediction[J].Oncotarget,2017,8(13):21187-21199.
7 Wu K,Yang L,Chen J,et al.miR-362-5p inhibits proliferation and migration of neuroblastoma cells by targeting phosphatidylinositol 3-kinase-C2β.[J].Febs Letter,2015,589(15):1911-1919.
8 Ni F,Gui Z,Guo Q,et al.downregulation of miR-362-5p inhibits proliferation,migration and invasion of human breast cancer MCF7 cells[J].Oncol Lett,2016,11(2):1155-1160.
9 Riddiford N,Schlosser G.six1 and eya1 both promote and arrest neuronal differentiation by activating multiple notch pathway genes[J].Developmental Biology,2017,431(2):152-167.
10 Li L,Liang Y,Kang L,et al.transcriptional regulation of the warburg effect in cancer by six1[J].Cancer Cell,2018,33(3):368-385.
11 Ma QL,Wang JH,Yang M,et al.mir-362-5p as a novel prognostic predictor of cytogenetically normal acute myeloid leukemia[J].J Transl Med,2018,16(1):68.
12 Wang D,Wang H,Li Y,et al.mir-362-3p functions as a tumor suppressor through targeting mcm5 in cervical adenocarcinoma[J].Biosci Rep,2018,38(3):20180668.
13 Kheirollahi M,Moodi M,Ashouri S,et al.evaluation of mir-362 expression in astrocytoma of human brain tumors:[J].Advanced Biomedical Research,2017,6(1):129.
14 Wu W,Ren Z,Li P,et al.six1:a critical transcription factor in tumorigenesis[J].Int J Cancer,2015,136(6):1245-1253.
15 He Z,Li G,Tang L,et al.six1 overexpression predicts poor prognosis and induces radioresistance through akt signaling in esophageal squamous cell carcinoma[J].Onco Targets Ther,2017,10:1071-1079.
16 Yu C,Zhang B,Li YL,et al.six1 reduces the expression of pten via activating pi3k/akt signal to promote cell proliferation and tumorigenesis in osteosarcoma.[J].Biomedicine Pharmacotherapy,2018,105:10-17.
17 Wei D,Ma X,Zhang S,et al.characterization of the promoter region of the bovine six1 gene:roles of myod,pax7,creb and myog[J].Sci Rep,2017,7(1):12599.

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[15]	王睿,余陈欢,方杰. miR-409-5p对肝癌细胞系HepG2增殖及迁移的影响[J]. 实用肿瘤学杂志, 2017, 31(4): 305-309.