miR-182对直肠癌细胞增殖、侵袭及Foxo3a/Wnt/β-catenin通路的调节作用

doi:10.11904/j.issn.1002-3070.2020.04.007

摘要/Abstract

摘要： 目的研究miR-182对直肠癌细胞增殖、侵袭及Foxo3a/Wnt/β-catenin通路的调节作用。方法收集2016年6月—2019年7月手术切除的直肠癌组织及癌旁组织,培养直肠癌细胞株HT29、SW620、HCT-116及正常肠上皮细胞HIEC,检测miR-182的表达量。将SW620细胞进行分组处理,对照组用不含药物的RPMI-1640培养基处理,NC组转染NC模拟物、miR-182组转染miR-182模拟物。采用MTS法检测各组细胞增殖活力,采用Transwell检测侵袭活力,采用Western blot检测Foxo3a/Wnt/β-catenin通路分子的表达。结果直肠癌组织中miR-182的表达量(2.14±0.55)明显高于癌旁组织(1.06±0.24)(P＜0.05);HT29、SW620、HCT-116细胞中miR-182的表达量明显高于HIEC(P＜0.05),且SW620细胞中miR-182表达增加最显著;miR-182组细胞的增殖活力(0.92±0.15)明显高于对照组(0.52±0.08)和NC组(0.55±0.07)(P＜0.05),侵袭数目(39.49±7.61)明显多于对照组(23.25±5.85)和NC组(21.84±4.77)(P＜0.05),迁移数目(44.12±9.29)明显多于对照组(29.39±6.18)和NC组(32.83±6.68)(P＜0.05);Foxo3a的表达水平(0.36±0.07)明显低于对照组(0.83±0.15)和NC组(0.86±0.12)(P＜0.05);Wnt2的表达水平(0.86±0.15)明显高于对照组(0.62±0.09)和NC组(0.58±0.07)(P＜0.05);β-catenin的表达水平(0.79±0.15)明显高于对照组(0.41±0.07)和NC组(0.45±0.08)(P＜0.05)。结论 miR-182能够促进直肠癌细胞的增殖和侵袭,其机制可能与靶向Foxo3a/Wnt/β-catenin通路相关。

关键词: 直肠癌, miR-182, 增殖, 侵袭, Foxo3a/Wnt/β-catenin通路

Abstract: Objective The aims of this study were to determine the effects of miR-182 on the proliferation and invasion of rectal cancer cells,and the regulation of Foxo3a/Wnt/β-catenin pathway. Methods Rectal cancer tissues and adjacent tissues that were surgically removed from June 2016 to July 2019 were collected,and human rectal cancer HT29,SW620,and HCT-116 cell lines and normal intestinal epithelial HIEC cells were cultured to detect the expression of miR-182.SW620 cells were treated in these following groups:the control group was treated with RPMI-1640 without drugs;the NC group was transfected with NC mimics and the miR-182 group was transfected with miR-182 mimics.The MTS assay was used to detect proliferation activity,Transwell was used to detect invasion activity,and Western blot was used to detect the expression of Foxo3a/Wnt/β-catenin pathway molecules in SW620 cells. Results The expression of miR-182 in rectal cancer tissues(2.14±0.55)was significantly higher than that in adjacent tissues(1.06±0.24)(P＜0.05);the expression of miR-182 in HT29,SW620 and HCT-116 cells were significantly higher than that in HIEC cells(P＜0.05),and the expression of miR-182 in SW620 cells increased most significantly;Proliferation activity in the miR-182 group(0.92±0.15)was significantly higher than that in the control group(0.52±0.08)and the NC group(0.55±0.07)(P＜0.05);The number of invasion in the miR-182 group(39.49±7.61)was significantly more than that of the control group(23.25±5.85)and the NC group(21.84±4.77)(P＜0.05);The number of migration in the miR-182 group(44.12±9.29)was significantly more than that in the control group(29.39±6.18)and the NC group(32.83±6.68)(P＜0.05);The expression of Foxo3a in the miR-182 group(0.36±0.07)was significantly lower than that in the control group(0.83±0.15)and the NC group(0.86±0.12)(P＜0.05);The expression of Wnt2 in the miR-182 group(0.86±0.15)was significantly higher than that in the control group(0.62±0.09)and the NC group(0.58±0.07)(P＜0.05);The expression of β-catenin in the miR-182 group(0.79±0.15)was significantly higher than that in the control group(0.41±0.07)and the NC group(0.45±0.08)(P＜0.05). Conclusion miR-182 can promote the proliferation and invasion of rectal cancer cells,and its mechanism may be related to targeting Foxo3a/Wnt/β-catenin pathway.

Key words: Rectal cancer, miR-182, Proliferation, Invasion, Foxo3a/Wnt/β-catenin pathway

中图分类号:

R656

陈灿, 张艳玲, 刘小庆, 冉凤伟. miR-182对直肠癌细胞增殖、侵袭及Foxo3a/Wnt/β-catenin通路的调节作用[J]. 实用肿瘤学杂志, 2020, 34(4): 328-333.

CHEN Can, ZHANG Yanling, LIU Xiaoqing, RAN Fengwei. The effect of miR-182 on the proliferation and invasion of rectal cancer cells and regulation of Foxo3a/Wnt/β-catenin pathway[J]. Journal of Practical Oncology, 2020, 34(4): 328-333.

0
/ / 推荐

导出引用管理器 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2020.04.007

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2020/V34/I4/328

参考文献

1 郭天安,谢丽,赵江,等.中国结直肠癌1988-2009年发病率和死亡率趋势分析[J].中华胃肠外科杂志,2018,21(1):33-40.
2 佟广海,田洋,吴华星.脂质组学在结直肠癌研究中的应用[J].实用肿瘤学杂志,2019,33(2):179-192.
3 Su Y,Zhang M,Zhang L,et al.Construction of an miRNA-mRNA regulatory network in colorectal cancer with bioinformatics methods[J].Anticancer Drugs,2019,30(6):588-595.
4 Liu X,Xu T,Hu X,et al.Elevated circulating miR-182 acts as a diagnostic biomarker for early colorectal cancer[J].Cancer Manag Res,2018,24(10):857-865.
5 余振兴,邓磊,张先斌,等.miR-182靶向调控FOXO3a表达对胶质瘤细胞增殖和侵袭能力的影响[J].安徽医科大学学报,2019,54(4):559-563.
6 Schneiderova M,Naccarati A,Pardini B,et al.MicroRNA-binding site polymorphisms in genes involved in colorectal cancer etiopathogenesis and their impact on disease prognosis[J].Mutagenesis,2017,32(5):533-542.
7 Yang Q,Wang R,Wei B,et al.Gene and microrna signatures are associated with the development and survival of glioblastoma patients[J].DNA Cell Biol,2019,38(7):688-699.
8 Zhao YS,Yang WC,Xin HW,et al.MiR-182-5p knockdown targeting PTEN inhibits cell proliferation and invasion of breast cancercells[J].Yonsei Med J,2019,60(2):148-157.
9 Li N,Nan CC,Zhong XY,et al.miR-182-5p promotes growth in oral squamous cell carcinoma by inhibiting CAMK2N1[J].Cell Physiol Biochem,2018,49(4):1329-1341.
10 Spitschak A,Meier C,Kowtharapu B,et al.MiR-182 promotes cancer invasion by linking RET oncogene activated NF-κB to loss of the HES1/Notch1 regulatory circuit[J].Mol Cancer,2017,16(1):24.
11 Chen G,Yu L,Dong H,et al.MiR-182 enhances radioresistance in non-small cell lung cancer cells by regulating FOXO3[J].Clin Exp Pharmacol Physiol,2019,46(2):137-143.
12 Cao MQ,You AB,Zhu XD,et al.miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a[J].J Hematol Oncol,2018,11(1):12.
13 Luo M,Wu C,Guo E,et al.FOXO3a knockdown promotes radioresistance in nasopharyngeal carcinoma by inducing epithelial-mesenchymal transition and the Wnt/β-catenin signaling pathway[J].Cancer Lett,2019,28(455):26-35.
14 Li J,Yang R,Dong Y,et al.Knockdown of FOXO3a induces epithelial-mesenchymal transition and promotes metastasis of pancreatic ductal adenocarcinoma by activation of the β-catenin/TCF4 pathway through SPRY2[J].J Exp Clin Cancer Res,2019,38(1):38.
15 郭存存,孙晋敏,韩文灿,等.结直肠癌中FOXO3a表达及其与β-catenin、E-cadherin关系[J].临床与实验病理学杂志,2013,29(7):737-741.

[1]	赵仁成, 林子棠, 余卫军, 雷林, 刘峥, 徐英, 郭艳芳, 彭绩. 2017—2019年深圳市宝安区40~74岁常住居民五癌风险流行状况分析[J]. 实用肿瘤学杂志, 2020, 34(4): 315-320.
[2]	李恒震, 张艳桥. 液体活检在结直肠癌诊断中的应用进展[J]. 实用肿瘤学杂志, 2020, 34(4): 357-361.
[3]	朱晓云, 张亚宁, 马碧萍. 1980—2018年上海市金山区结直肠癌死亡水平及其所致早死概率的趋势分析[J]. 实用肿瘤学杂志, 2020, 34(3): 198-202.
[4]	张遥, 范丹. 长链非编码RNA PSMA3-AS1在人胶质瘤细胞中的表达及作用研究[J]. 实用肿瘤学杂志, 2020, 34(3): 214-219.
[5]	鲁雪梅, 李云涛, 安锦慧, 季国忠. 溶血磷脂酸在结直肠癌发生发展中的机制研究[J]. 实用肿瘤学杂志, 2020, 34(3): 276-281.
[6]	王飞, 朱贲贲. 丙泊酚经HIF-1α信号通路对头颈鳞状细胞癌SCC-74细胞增殖、凋亡与侵袭的影响[J]. 实用肿瘤学杂志, 2020, 34(2): 120-125.
[7]	刘光霞, 赵连春, 陈芳, 贾乾, 高伟, 侯瞻, 卢亚敏. ZCCHC12对甲状腺细胞恶性转化的影响与作用机制[J]. 实用肿瘤学杂志, 2020, 34(2): 133-138.
[8]	王璞, 韦丽宾, 倪广晓. CCNB1基因通过调控PI3K/Akt信号通路对口腔鳞癌细胞增殖、侵袭和迁移的影响[J]. 实用肿瘤学杂志, 2020, 34(2): 144-149.
[9]	张从义, 崔逸峰, 李宝宝, 刘连新. 细胞分裂周期7蛋白在肝癌组织的表达及其对肝癌细胞增殖和侵袭的影响[J]. 实用肿瘤学杂志, 2020, 34(2): 150-155.
[10]	张巍, 姜晓东, 迟大鹏. WNT4在脑胶质瘤中甲基化下调及抑制恶性胶质瘤细胞增殖的研究[J]. 实用肿瘤学杂志, 2020, 34(2): 156-162.
[11]	李斌, 冯保恒, 尹富霞, 苏伟. 建立结直肠癌移植瘤模型研究小鼠肠道中细菌感染情况及地西他滨联合顺铂化疗的作用机制[J]. 实用肿瘤学杂志, 2020, 34(2): 163-168.
[12]	杨东明, 卢庆刚. 直肠癌术前在无均整块器模式下容积弧形调强与固定野调强放疗计划的剂量学比较[J]. 实用肿瘤学杂志, 2020, 34(2): 181-184.
[13]	曾理, 庄树彤, 丁世华, 陈冲, 焦璐, 孙大勇. 长链非编码RNA AFAP1-AS1通过PTEN/p-AKT信号通路调控结直肠癌细胞增殖的分子机制研究[J]. 实用肿瘤学杂志, 2020, 34(1): 11-16.
[14]	赵楠楠, 秦文, 韩永焕, 鲁静, 李亚敏, 徐亚君. SOX11 抑制食管癌细胞增殖和迁移的机制研究[J]. 实用肿瘤学杂志, 2020, 34(1): 17-23.
[15]	赵云霞, 牛波. LncRNA NBAT1通过调控miR-3664-5p/Caspase 9分子轴对人乳腺癌细胞增殖的影响[J]. 实用肿瘤学杂志, 2020, 34(1): 24-29.