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