Journal of Surgery Concepts & Practice >
Study on microRNA-9-5p reducing sensitivity of breast cancer cells to doxorubicin through targeting HIC1
Received date: 2019-11-04
Online published: 2020-05-25
Objective To study the effect of microRNA-9-5p (miR-9-5p) which regulate hypermethylated in cancer 1 (HIC1) in reducing sensitivity of breast cancer MDA-MB-231 cells to doxorubicin (DOX) and the mechanisms. Methods ①Up-regulation or down-regulation of miR-9-5p in cells was constructed by lentivirus transfection. Cell viability and apoptosis were detected with CCK-8 and flow cytometry after adding different concentrations of DOC. ②Expression of HIC1 was detected by reverse transcription-polymerase chain reaction and Western blotting when miRNA-9-5p was overexpressed or inhibited. The interaction between miR-9-5p and HIC1 was analyzed by database and luciferase assay. ③HIC1 was down-regulated to detect cell viability and apoptosis after adding different concentrations of DOX. Results ①Up-regulation of miR-9-5p increased cell viability, and reduced apoptosis. Down-regulation of miR-9-5p reduced cell viability and increased apoptosis. ②miR-9-5p directly targeted HIC1 and negative relationship of expression was present between miR-9-5p and HIC1. ③Down-regulation of HIC1 could reverse the down-regulation effect of miR-9-5p. Conclusions miR-9-5p reduces the sensitivity of breast cancer cells to DOX through down-regulation of HIC1.
Key words: Breast cancer; MicroRNA-9-5p; Hypermethylated in cancer 1; Doxorubicin; Sensitivity
GAO Hang, ZHAO Feng, WU Yan, PEI Wenjiang, ZHONG Ming, GU Yan, GUO Shanyu, DAI Qiancheng, ZHANG Wei . Study on microRNA-9-5p reducing sensitivity of breast cancer cells to doxorubicin through targeting HIC1[J]. Journal of Surgery Concepts & Practice, 2020 , 25(03) : 227 -233 . DOI: 10.16139/j.1007-9610.2020.03.011
| [1] | Adachi Y, Yoshimura M, Nishida K, et al. Acute phase dynamics of circulating tumor cells after paclitaxel and doxorubicin chemotherapy in breast cancer mouse models[J]. Breast Cancer Res Treat, 2018, 167(2):439-450. |
| [2] | Zhang Y, Xia F, Zhang F, et al. miR-135b-5p enhances doxorubicin-sensitivity of breast cancer cells through targeting anterior gradient 2[J]. J Exp Clin Cancer Res, 2019, 38(1):26. |
| [3] | Chewchuk S, Guo B, Parissenti AM. Alterations in estrogen signaling pathways upon acquisition of anthracycline resistance in breast tumor cells[J]. PLoS One, 2017, 12(2):e0172244. |
| [4] | Liu DZ, Chang B, Li XD, et al. MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1[J]. Clin Transl Oncol, 2017, 19(9):1133-1140. |
| [5] | Zhao F, Pan S, Gu Y, et al. Reactivation of HIC1 gene by saRNA inhibits clonogenicity and invasiveness in breast cancer cells[J]. Oncol lett, 2015, 9(1):159-164. |
| [6] | Feng F, Zhu X, Wang C, et al. Downregulation of hypermethylated in cancer-1 by miR-4532 promotes adria-mycin resistance in breast cancer cells[J]. Cancer Cell Int, 2018, 18:127. |
| [7] | Rivankar S. An overview of doxorubicin formulations in cancer therapy[J]. J Cancer Res and Ther, 2014, 10(4):853-858. |
| [8] | Wang S, Oh DY, Leventaki V, et al. MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer[J]. Cancer Lett, 2019,465:12-23. |
| [9] | Lin H, Gregory JH. MicroRNAs: small RNAs with a big role in gene regulation[J]. Nat Rev Genet, 2004, 5(7):522-531. |
| [10] | Dong H, Lei J, Ding L, et al. MicroRNA: function, detection, and bioanalysis[J]. Chem Rev, 2013, 113(8):6207-6233. |
| [11] | Piasecka D, Braun M, Kordek R, et al. MicroRNAs in regulation of triple-negative breast cancer progression[J]. J Cancer Res Clin Oncol, 2018, 144(8):1401-1411. |
| [12] | Gulyaeva LF, Kushlinskiy NE. Regulatory mechanisms of microRNA expression[J]. J Transl Med, 2016, 14(1):143. |
| [13] | Rivera-Barahona A, Pérez B, Richard E, et al. Role of miRNAs in human disease and inborn errors of metabolism[J]. J Inherit Metab Dis, 2017, 40(4):471-480. |
| [14] | Madelaine R, Sloan SA, Huber N, et al. MicroRNA-9 couples brain neurogenesis and angiogenesis[J]. Cell Rep, 2017, 20(7):1533-1542. |
| [15] | Li G, Wu F, Yang H, et al. MiR-9-5p promotes cell growth and metastasis in non-small cell lung cancer through the repression of TGFBR2[J]. Biomed Pharmacother, 2017, 96:1170-1178. |
| [16] | Sondermann A, Andreghetto FM, Moulatlet AC, et al. MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer[J]. Clin Exp Metastasis, 2015, 32(6):521-530. |
| [17] | Yi J, Gao ZF. MicroRNA-9-5p promotes angiogenesis but inhibits apoptosis and inflammation of high glucose-induced injury in human umbilical vascular endothelial cells by targeting CXCR4[J]. Int J Biol Macromol, 2019, 130:1-9. |
| [18] | Zhang H, Zhang Z, Wang S, et al. The mechanisms involved in miR-9 regulated apoptosis in cervical cancer by targeting FOXO3[J]. Biomed Pharmacother, 2018,102:626-632. |
| [19] | Wang H, Zhang W, Zuo Y, et al. miR-9 promotes cell proliferation and inhibits apoptosis by targeting LASS2 in bladder cancer[J]. Tumour Biol, 2015, 36(12):9631-9640. |
| [20] | Polley E, Kunkei M, Evans D, et al. Small cell lung cancer screen of oncology drugs, investigational agents, and gene and microRNA expression[J]. J Natl Cancer Inst, 2016, 108(10) |
| [21] | Barbano R, Pasculli B, Rendina M, et al. Stepwise analysis of MIR9 loci identifies miR-9-5p to be involved in Oestrogen regulated pathways in breast cancer patients[J]. Sci Rep, 2017, 7:45283. |
| [22] | Wales MM, Biel MA, Deiry WE, et al. p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3[J]. Nat Med, 1995, 1(6):570-577. |
| [23] | Szczepny A, Carey K, Mckenzie L, et al. The tumor suppressor Hic1 maintains chromosomal stability independent of Tp53[J]. Oncogene, 2018, 37(14):1939-1948. |
| [24] | Li P, Liu X, Dong ZM, et al. Epigenetic silencing of HIC1 promotes epithelial-mesenchymal transition and drives progression in esophageal squamous cell carcinoma[J]. Oncotarget, 2015, 6(35):38151-38165. |
| [25] | Zhou X, Zhang P, Han H, et al. Hypermethylated in cancer 1 (HIC1) suppresses bladder cancer progression by targeting yes-associated protein (YAP) pathway[J]. J Cell Biochem, 2019, 120(4):6471-6481. |
/
| 〈 |
|
〉 |