丹参酚酸B靶向SOX2OT/miRNA-34a/SOX2轴抑制大肠癌细胞侵袭转移

汤中杰; 汪鑫; 郭飘婷

doi:10.3969/j.issn.1671-038X.2021.02.05

丹参酚酸B靶向SOX2OT/miRNA-34a/SOX2轴抑制大肠癌细胞侵袭转移

- 1 温州市中心医院化疗科2(浙江温州, 325000);
- 2 浙江中医药大学附属第二医院普外科;
- 3 浙江中医药大学附属第二医院全科医学科
基金项目:
国家自然科学基金青年项目(No:81803876)

详细信息

通讯作者: 郭飘婷,E-mail:522135842@qq.com

中图分类号: R735.3

收稿日期: 2020-09-02

Salvianolic acid B inhibits invasion and metastasis of colorectal cancer cells by targeting SOX2OT/miR-34a/SOX2 axis

- 1 Department of Chemotherapy 2, Wenzhou Central Hospital, Wenzhou, 325000, China;
- 2 Department of Surgery, the Second Affiliated Hospital of Zhejiang Chinese Medical University;
- 3 Department of General Medicine, the Second Affiliated Hospital of Zhejiang Chinese Medical University

More Information

Corresponding author: GUO Piaoting, E-mail: 522135842@qq.com

Received Date: 02 September 2020

摘要

摘要: 目的:验证SOX2OT/miRNA(miR)-34a/SOX2信号轴对人大肠癌LOVO细胞侵袭转移的影响以及丹参酚酸B(SalB)通过该信号轴浓度依赖性抑制LOVO细胞侵袭转移。方法:双荧光素酶报告基因检测SOX2OT与miR-34a、miR-34a与SOX2的靶向结合;瞬时转染SOX2OT质粒和miR-34a mimic至LOVO细胞,RT-qPCR验证转染效率;RT-qPCR、Western blot检测SOX2OT、miR-34a与SOX2三者表达的相关性;划痕实验、Transwell实验检测SOX2OT/miR-34a/SOX2轴对LOVO细胞侵袭迁移的影响;MTT法检测丹参酚酸B对LOVO生长抑制作用;RT-qPCR检测低、中、高浓度丹参酚酸B处理下SOX2OT的表达;划痕实验、Transwell实验检测低、中、高剂量丹参酚酸B作用时细胞侵袭迁移情况。结果:LOVO细胞中SOX2OT与miR-34a、miR-34a与SOX2之间存在靶向结合;SOX2OT抑制miR-34a,上调SOX2;miR-34a可下调SOX2OT和SOX2表达;miR-34a逆转SOX2OT对细胞侵袭和迁移能力的增强作用;在一定浓度范围内丹参酚酸B量效相关性抑制LOVO细胞生长;丹参酚酸B浓度依赖性抑制LOVO细胞SOX2OT表达;丹参酚酸B抑制LOVO细胞侵袭转移,且随着浓度增加,抑制作用增强。结论:SOX2OT/miR-34a/SOX2信号轴与LOVO细胞侵袭转移密切相关,丹参酚酸B通过抑制该信号轴量效相关性抑制LOVO细胞侵袭转移。
- 丹参酚酸B /
- SOX2OT/miR-34a/SOX2轴 /
- 大肠癌 /
- 侵袭转移 /
- LOVO细胞
Abstract: Objective: To verify the effect of SOX2 OT/miR-34 a/SOX2 signal axis on the invasion and metastasis of human colorectal cancer LOVO cells, and that Salvianolic acid B(SalB) concentration-dependently inhibits the invasion and metastasis of LOVO cells through the signal axis.Methods: Dual Luciferase Reporter Gene Assay was used to verify the targeted binding of SOX2 OT to miR-34 a and miR-34 a to SOX2; SOX2 OT plasmid and miR-34 a mimic were transient transfected into LOVO cells, RT-qPCR was used to verify the transfection efficiency; RT-qPCR and Western blot were used to detect the correlation between SOX2 OT, miR-34 a and SOX2 expression; Scratch test and transwell test were used to detect the effects of SOX2 OT/miR-34 a/SOX2 axis on invasion and migration of LOVO cells; MTT assay was used to detect the inhibitory effect of Salvianolic acid B on LOVO growth; The expression of SOX2 OT was detected by RT-qPCR after treatment with low, medium and high dosages of Salvianolic acid B; Scratch test and transwell test were used to detect the invasion and migration of cells treated with Salvianolic acid B at low, medium and high dosages.Results: There were targeting relationship between SOX2 OT and miR-34 a, and between miR-34 a and SOX2 in LOVO cells; SOX2 OT inhibited miR-34 a and upregulated SOX2; MiR-34 a could down regulate the expression of SOX2 OT and SOX2; MiR-34 a reversed the enhancement of SOX2 OT on cell invasion and migration; Salvianolic acid B inhibited the growth of LOVO cells in dose-dependent manner within a certain concentration range; Salvianolic acid B inhibits SOX2 OT expression in a concentration dependent manner; Salvianolic acid B inhibited the invasion and metastasis of LOVO cells, and the inhibitory effect increased with the increase of concentration.Conclusion: SOX2 OT/miR-34 a/SOX2 signal axis is closely related to the invasion and metastasis of LOVO cells, Salvianolic acid B inhibits the invasion and metastasis of LOVO cells by inhibiting this signal axis.
- salB /
- SOX2OT/miR-34a/SOX2 axis /
- colorectal cancer /
- invasion and metastasis /
- LOVO cells

HTML全文

参考文献(17)

[1]	Li X,Zhang Q,Zhao L,et al.A Combined four-mRNA Signature Associated with Lymphatic Metastasis for Prognosis of Colorectal Cancer[J].J Cancer,2020,11(8):2139-2149.
[2]	Chen BB.Will novel imaging approaches predict oligometastases or early liver metastasis in patients with colorectal cancer?[J].Hepatobiliary Surg Nutr,2020,9(3):391-393.
[3]	Lu X,Wu X,Jing L,et al.Network Pharmacology Analysis and Experiments Validation of the Inhibitory Effect of JianPi Fu Recipe on Colorectal Cancer LoVo Cells Metastasis and Growth[J].Evid Based Complement Alternat Med,2020,2020:4517483.
[4]	林明生,杨舒瑾.中医药治疗大肠癌的研究进展[J].光明中医,2020,35(14):2270-2272.
[5]	严春红,杨玮丽,李学和.lncRNA SOX2OT在卵巢癌细胞系中的表达及其对卵巢癌生物学行为的影响[J].中华全科医学,2020,18(6):930-933.
[6]	Zhan Y,Chen Z,He S,et al.Long non-coding RNA SOX2OT promotes the stemness phenotype of bladder cancer cells by modulating SOX2[J].Mol Cancer,2020,19(1):25.
[7]	Liang Y,Zhang D,Zheng T,et al.lncRNA-SOX2OT promotes hepatocellular carcinoma invasion and metastasis through miR-122-5p-mediated activation of PKM2[J].Oncogenesis,2020,9(5):54.
[8]	Guo P,Wang S,Liang W,et al.Salvianolic acid B reverses multidrug resistance in HCT-8/VCR human colorectal cancer cells by increasing ROS levels[J].Mol Med Rep,2017,15(2):724-730.
[9]	Guo P,Wang J,Gao W,et al.Salvianolic acid B reverses multidrug resistance in nude mice bearing human colon cancer stem cells[J].Mol Med Rep,2018,18(2):1323-1334.
[10]	Liu B,Zhou J,Wang C,et al.LncRNA SOX2OT promotes temozolomide resistance by elevating SOX2 expression via ALKBH5-mediated epigenetic regulation in glioblastoma[J].Cell Death Dis,2020,11(5):384.
[11]	Shafiee M,Aleyasin SA,Vasei M,et al.Down-Regulatory Effects of miR-211 on Long Non-Coding RNA SOX2OT and SOX2 Genes in Esophageal Squamous Cell Carcinoma[J].Cell J,2016,17(4):593-600.
[12]	蔡鲍平,余昌俊,吴文涌.LncRNA HOXC-AS3通过miR-15b-5p/E2F3生物学轴促进胃癌细胞的增殖和迁移[J].中国癌症杂志,2020,30(6):407-418.
[13]	向涵,刘铮,周毅彬,等.lncRNA ZBED3-AS1通过吸附miR-512-5p调控DACH1抑制前列腺癌细胞的增殖和迁移[J].临床与实验病理学杂志,2020,36(4):401-406.
[14]	Huang S,Zhu Y,Wang C,et al.PAK5 facilitates the proliferation,invasion and migration in colorectal cancer cells[J].Cancer Med,2020,9(13):4777-4790.
[15]	杨庆华,陈栋.蒲公英提取物调控DPC4对大肠癌细胞凋亡、迁移、侵袭的影响及其机制研究[J].新中医,2020,52(8):1-5.
[16]	Zhang M,Jiang X,Jiang S,et al.LncRNA FOXD2-AS1 Regulates miR-25-3p/Sema4c Axis To Promote The Invasion And Migration Of Colorectal Cancer Cells[J].Cancer Manag Res,2019,11:10633-10639.
[17]	贾茹,张影茹,邵诗芸,等.补肾解毒散结方调控JAK/STAT3信号通路抑制大肠癌侵袭转移的研究[J].中华中医药杂志,2020,35(3):1433-1436.