Advanced Search
GAO Hongyan, GUO Jie, WU Fangxiong, LIU Fengrui, WANG Li. Mechanism of miRNA-451 Regulating Resistance of Gastric Cancer Cells to 5-Fu Through MRP[J]. Cancer Research on Prevention and Treatment, 2019, 46(12): 1073-1077. DOI: 10.3971/j.issn.1000-8578.2019.19.0618
Citation: GAO Hongyan, GUO Jie, WU Fangxiong, LIU Fengrui, WANG Li. Mechanism of miRNA-451 Regulating Resistance of Gastric Cancer Cells to 5-Fu Through MRP[J]. Cancer Research on Prevention and Treatment, 2019, 46(12): 1073-1077. DOI: 10.3971/j.issn.1000-8578.2019.19.0618

Mechanism of miRNA-451 Regulating Resistance of Gastric Cancer Cells to 5-Fu Through MRP

More Information
  • Corresponding author:

    LIU Fengrui, E-mail: 842689415@qq.com

  • Received Date: May 12, 2019
  • Revised Date: October 07, 2019
  • Available Online: January 12, 2024
  • Objective 

    To investigate the mechanism of miR-451 regulating the resistance of gastric cancer to 5-Fu by down-regulating the expression of MRP.

    Methods 

    Real-time quantitative PCR was used to detect the relative expression of miR-451 in 20 pairs of human gastric cancer tissues and adjacent tissues and gastric cancer cell lines. The expression of miR-451 in the resistance group and non-resistant group were detected. We constructed gastric cancer cell line with stable plent-miR-451 overexpression, and the overexpression efficiency of miR-451 in gastric cancer cell line was detected by real-time quantitative PCR. The proliferation activity of the cells was detected by CCK8. The miR-451 target gene was analyzed by bioinformatics method and verified by luciferase assay. The effect of miR-451 on the mRNA and protein of targeted gene MRP were detected by real-time quantitative PCR and Western blot.

    Results 

    The expression of miR-451 in normal tissues was higher than that in cancer tissues, and miR-451 expression in the non-resistant gastric cancer tissues was higher than that in the drug-resistant gastric cancer tissues. The overexpression of miR-451 reduced the resistance of gastric cancer cells to 5-Fu treatment (P=0.0006). Bioinformatics analysis showed that MRP was the target gene of miR-451. Luciferase assay also confirmed that MRP was a potential target gene of miR-451. miR-451 overexpression decreased the mRNA and protein of the drug resistance gene MRP (P=0.00069).

    Conclusion 

    Overexpression of miR451 could down-regulate MRP expression, which reduces the resistance of tumor cells to 5-Fu.

  • [1]
    Zhu ZM, Li ZR, Huang Y, et al. DJ-1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway[J]. Oncol Rep, 2014, 31(3): 1489-1497. doi: 10.3892/or.2013.2961
    [2]
    Fang Q, Chen XY, Zhi XT. Long Non-Coding RNA (LncRNA) Urothelial Carcinoma Associated 1 (UCA1) Increases Multi-Drug Resistance of Gastric Cancer via Downregulating miR-27b[J]. Med Sci Monit, 2016, 22: 3506-3513. doi: 10.12659/MSM.900688
    [3]
    Wong KM, Qiu X, Cheng D, et al. Two BRM promoter insertion polymorphisms increase the risk of early-stage upper aerodigestive tract cancers[J]. Cancer Med, 2014, 3(2): 426-433. doi: 10.1002/cam4.201
    [4]
    Xu X, Zhang Y, Li W, et al. Wogonin reverses multi-drug resistance of human myelogenous leukemia K562/A02 cells via downregulation of MRP1 expression by inhibiting Nrf2/ARE signaling pathway[J]. Biochem Pharmacol, 2014, 92(2): 220-234. doi: 10.1016/j.bcp.2014.09.008
    [5]
    Chen YL, Yang TY, Chen KC, et al. Hypoxia can impair doxorubicin resistance of non-small cell lung cancer cells by inhibiting MRP1 and P-gp expression and boosting the chemosensitizing effects of MRP1 and P-gp blockers[J]. Cell Oncol(Dordr), 2016, 39(5): 411-433. doi: 10.1007/s13402-016-0285-5
    [6]
    Syngal S, Brand RE, Church JM, et al. ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes[J]. Am J Gastroenterol, 2015, 110(2): 223-262. doi: 10.1038/ajg.2014.435
    [7]
    Ebrahimi S, Hashemy SI. MicroRNA-mediated redox regulation modulates therapy resistance in cancer cells: clinical perspectives[J]. Cell Oncol(Dordr), 2019, 42(2): 131-141. doi: 10.1007/s13402-018-00421-z
    [8]
    Tsuchiya S, Oku M, Imanaka Y, et al. MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells[J]. Nucleic Acids Res, 2009, 37(11): 3821-3827. doi: 10.1093/nar/gkp255
    [9]
    Ribeiro-dos-Santos Â, Khayat AS, Silva A, et al. Ultra-Deep Sequencing Reveals the microRNA Expression Pattern of the Human Stomach[J]. PloS One, 2010, 5(10): e13205. doi: 10.1371/journal.pone.0013205
    [10]
    Goto A, Tanaka M, Yoshida M, et al. The low expression of miR-451 predicts a worse prognosis in non-small cell lung cancer cases[J]. PloS One, 2017, 12(7): e0181270. doi: 10.1371/journal.pone.0181270
    [11]
    Liu K, Tian H, Zhang Y, et al. miR-451 selectively increases sensitivity to cisplatin in ERCC1-high non-small cell lung cancer cells[J]. J Cell Biochem, 2018.[Epub ahead of print] http://cn.bing.com/academic/profile?id=ca3f997ac7d7cbf9d994e9156e3659c2&encoded=0&v=paper_preview&mkt=zh-cn
    [12]
    Keshavarzi Z, Janghorban R, Alipour S, et al. The effect of vitamin D and E vaginal suppositories on tamoxifen-induced vaginal atrophy in women with breast cancer[J]. Support Care Cancer, 2019, 27(4): 1325-1334. doi: 10.1007/s00520-019-04684-6
    [13]
    O'Meara JA, Jakalian A, LaPlante S, et al. Scaffold hopping in the rational design of novel HIV-1 non-nucleoside reverse transcriptase inhibitors[J]. Bioorg Med Chem Lett, 2007, 17(12): 3362-3366. doi: 10.1016/j.bmcl.2007.03.097
    [14]
    Boumendjel A, Baubichon-Cortay H, Trompier D, et al. Anticancer multidrug resistance mediated by MRP1: Recent advances in the discovery of reversal agents[J]. Med Res Rev, 2005, 25(4): 453-472. doi: 10.1002/med.20032
  • Related Articles

    [1]HAN Zheng, HUANG Xiaodong, LIU Meng, ZHU Qingxi, TAN Jie, LIU Weijie, CHEN Wei, ZOU Yanli, CAI Yishan, HUANG Shasha, TIAN Xia. Effect of Noscapine on Drug Resistance of 5-Fluorouracil-resistant Human Colon Cancer Cell Lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu[J]. Cancer Research on Prevention and Treatment, 2019, 46(8): 696-701. DOI: 10.3971/j.issn.1000-8578.2019.18.1927
    [2]FENG Liping, SU Wenmei, XIAN Feng, LUO Liang. miR-143/145 Cluster Regulate Multi-drug Resistance of Small Cell Lung Cancer[J]. Cancer Research on Prevention and Treatment, 2016, 43(5): 326-330. DOI: 10.3971/j.issn.1000-8578.2016.05.002
    [3]WEI Ling, SONG Xian-rang, SUN Ju-jie, WANG Xing-wu, SONG Bao, ZHENG Yan. Drug Resistance Reversal of Doxorubicin-resistant Human Leukemia Cell Line K562/ADM through Down-regulating MDR1 Gene[J]. Cancer Research on Prevention and Treatment, 2010, 37(05): 515-518. DOI: 10.3971/j.issn.1000-8578.2010.05.007
    [4]TAN Wen-fu, WU Xu-feng, CHEN Hui-zhen. Expression and Signif icance of CD44v6 and MRP in Ovarian Carcinoma[J]. Cancer Research on Prevention and Treatment, 2005, 32(12): 755-757. DOI: 10.3971/j.issn.1000-8578.592
    [5]GUI Xian, LIU Hui-min, HE Jin, LI Yu-li, SUN Jing, YU Hong-yu. Expression and Clinical Significance of LRP and MRP in Human Colorectal Carcinomas[J]. Cancer Research on Prevention and Treatment, 2005, 32(08): 499-501. DOI: 10.3971/j.issn.1000-8578.788
    [6]FAN Hai-ning, HUANG Tao. Antisense RNA of survivin Enhances the Sensitivity of PANC-1 Cell to 5-Fu[J]. Cancer Research on Prevention and Treatment, 2005, 32(05): 279-281. DOI: 10.3971/j.issn.1000-8578.1273
    [7]CHEN Xin, LIN Wen bo, SHEN You zhu. The Influence of Thymidylate Synthase (TS) in Colon Carcinoma used 5-Fu Cure Prospective Study[J]. Cancer Research on Prevention and Treatment, 2004, 31(08): 480-481. DOI: 10.3971/j.issn.1000-8578.3182
    [8]ZHOU Jian-hua, ZHANG Li-chen, LU Hai-bo, et al. Short-term response of continuous infusion of 5-Fu in advanced gastric carcinoma[J]. Cancer Research on Prevention and Treatment, 2003, 30(06): 500-501. DOI: 10.3971/j.issn.1000-8578.2922
    [9]Wu Hui, Huang Xuezhen, Xie Xianhe. Estimating the Short-term Effect of CF. 5-Fu and DDP in Treating Advanced Nasopharygeal Carcinona[J]. Cancer Research on Prevention and Treatment, 1999, 26(3): 217-218.
    [10]Bu Xing-Yao, . Multidrug Resistance and Reversion study on Human Neuroblastoma SK-H-SN Cell Line[J]. Cancer Research on Prevention and Treatment, 1997, 24(1): 10-12.

Catalog

    WANG Li

    1. On this Site
    2. On Google Scholar
    3. On PubMed
    Article views (2066) PDF downloads (484) Cited by()

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return