MicroRNA‑598 inhibits the growth of triple negative breast cancer cells by targeting JAG1

Han,Guohui; Bai,Xiangdong; Jiang,Hongchuan; He,Qiang

doi:10.3892/etm.2021.9666

MicroRNA‑598 inhibits the growth of triple negative breast cancer cells by targeting JAG1

Authors:
- Guohui Han
- Xiangdong Bai
- Hongchuan Jiang
- Qiang He
View Affiliations

Affiliations: Department of Breast Surgery, Shanxi Provincial Cancer Hospital, Shanxi Medical University, Taiyuan, Shanxi 030013, P.R. China, Department of Breast Surgery, Beijing Chaoyang Hospital, The Affiliated Hospital of Capital Medical University, Beijing 100020, P.R. China, Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, The Affiliated Hospital of Capital Medical University, Beijing 100020, P.R. China
Published online on: January 21, 2021 https://doi.org/10.3892/etm.2021.9666
Article Number: 235
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Triple‑negative breast cancer (TNBC) has an aggressive phenotype and a poor outcome. The discovery that dysregulated microRNAs (miRNAs) play an important role in tumor progression has led to the suggestion that miRNAs (miRs) could be a potential target for the treatment of TNBC. In the present study, it was demonstrated that miR‑598 expression was significantly decreased in TNBC tissues and was related to the degree of lymph node metastasis of patients with TNBC. Ectopic expression of miR‑598 suppressed viability and colony formation, as well as increased the apoptosis of TNBC cells. To further understand the functional mechanism of action underlying miR‑598 in TNBC, targets of miR‑598 were predicted with the miRDB bioinformatics tool. Jagged 1 (JAG1) was identified as a direct target of miR‑598, possessing a binding site for miR‑598 in its 3'‑untranslated region. Overexpression of miR‑598 inhibited the expression of JAG1 in TNBC cells. In addition, JAG1 was highly expressed in TNBC tissues and its expression was negatively correlated with the expression of miR‑598. Overexpression of JAG1 significantly attenuated the inhibitory effects of miR‑598 on the proliferation and colony formation of TNBC cells. Collectively, these results provided novel insights into the functional mechanism of action for the miR‑598/JAG1 pathway in the development of TNBC.

View Figures

View References

1	Tariq K and Rana F: TNBC vs. Non-TNBC: A five-year retrospective review of differences in mean age, family history, smoking history and stage at diagnosis at an Inner City University Program. World J Oncol. 4:241–247. 2013.PubMed/NCBI View Article : Google Scholar
2	Bianchini G, Balko JM, Mayer IA, Sanders ME and Gianni L: Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 13:674–690. 2016.PubMed/NCBI View Article : Google Scholar
3	Jhan JR and Andrechek ER: Triple-negative breast cancer and the potential for targeted therapy. Pharmacogenomics. 18:1595–1609. 2017.PubMed/NCBI View Article : Google Scholar
4	Nakhjavani M, Hardingham JE, Palethorpe HM, Price TJ and Townsend AR: Druggable Molecular Targets for the Treatment of Triple Negative Breast Cancer. J Breast Cancer. 22:341–361. 2019.PubMed/NCBI View Article : Google Scholar
5	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004.PubMed/NCBI View Article : Google Scholar
6	Mohr AM and Mott JL: Overview of microRNA biology. Semin Liver Dis. 35:3–11. 2015.PubMed/NCBI View Article : Google Scholar
7	Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 79:351–379. 2010.PubMed/NCBI View Article : Google Scholar
8	Qu H, Xu W, Huang Y and Yang S: Circulating miRNAs: Promising biomarkers of human cancer. Asian Pac J Cancer Prev. 12:1117–1125. 2011.PubMed/NCBI
9	Momtazi AA, Shahabipour F, Khatibi S, Johnston TP, Pirro M and Sahebkar A: Curcumin as a microRNA regulator in cancer: A review. Rev Physiol Biochem Pharmacol. 171:1–38. 2016.PubMed/NCBI View Article : Google Scholar
10	Iorio MV and Croce CM: MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 9(852)2017.PubMed/NCBI View Article : Google Scholar
11	Kwak PB, Iwasaki S and Tomari Y: The microRNA pathway and cancer. Cancer Sci. 101:2309–2315. 2010.PubMed/NCBI View Article : Google Scholar
12	Rupaimoole R and Slack FJ: MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 16:203–222. 2017.PubMed/NCBI View Article : Google Scholar
13	Piasecka D, Braun M, Kordek R, Sadej R and Romanska H: MicroRNAs in regulation of triple-negative breast cancer progression. J Cancer Res Clin Oncol. 144:1401–1411. 2018.PubMed/NCBI View Article : Google Scholar
14	Petrovic N, Davidovic R, Bajic V, Obradovic M and Isenovic RE: MicroRNA in breast cancer: The association with BRCA1/2. Cancer Biomark. 19:119–128. 2017.PubMed/NCBI View Article : Google Scholar
15	Wang C, Xu C, Niu R, Hu G, Gu Z and Zhuang Z: miR-890 inhibits proliferation and invasion and induces apoptosis in triple-negative breast cancer cells by targeting CD147. BMC Cancer. 19(577)2019.PubMed/NCBI View Article : Google Scholar
16	Zhang Y, Zhao Z, Li S, Dong L, Li Y, Mao Y, Liang Y, Tao Y and Ma J: Inhibition of miR 214 attenuates the migration and invasion of triple negative breast cancer cells. Mol Med Rep. 19:4035–4042. 2019.PubMed/NCBI View Article : Google Scholar
17	Ma Y, Yan F, Wei W, Deng J, Li L, Liu L and Sun J: MicroRNA-598 inhibits the growth and maintenance of gastric cancer stem-like cells by down-regulating RRS1. Cell Cycle. 18:2757–2769. 2019.PubMed/NCBI View Article : Google Scholar
18	Tong X, Su P, Yang H, Chi F, Shen L, Feng X, Jiang H, Zhang X and Wang Z: MicroRNA-598 inhibits the proliferation and invasion of non-small cell lung cancer cells by directly targeting ZEB2. Exp Ther Med. 16:5417–5423. 2018.PubMed/NCBI View Article : Google Scholar
19	Chen J, Zhang H, Chen Y, Qiao G, Jiang W, Ni P, Liu X and Ma L: miR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT. Exp Cell Res. 352:104–112. 2017.PubMed/NCBI View Article : Google Scholar
20	Shimizu K, Chiba S, Saito T, Kumano K and Hirai H: Physical interaction of Delta1, Jagged1, and Jagged2 with Notch1 and Notch3 receptors. Biochem Biophys Res Commun. 276:385–389. 2000.PubMed/NCBI View Article : Google Scholar
21	Grochowski CM, Loomes KM and Spinner NB: Jagged1 (JAG1): Structure, expression, and disease associations. Gene. 576:381–384. 2016.PubMed/NCBI View Article : Google Scholar
22	Choi K, Ahn YH, Gibbons DL, Tran HT, Creighton CJ, Girard L, Minna JD, Qin FX and Kurie JM: Distinct biological roles for the notch ligands Jagged-1 and Jagged-2. J Biol Chem. 284:17766–17774. 2009.PubMed/NCBI View Article : Google Scholar
23	Zavadil J, Cermak L, Soto-Nieves N and Böttinger EP: Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J. 23:1155–1165. 2004.PubMed/NCBI View Article : Google Scholar
24	Chen X, Stoeck A, Lee SJ, Shih IeM, Wang MM and Wang TL: Jagged1 expression regulated by Notch3 and Wnt/β-catenin signaling pathways in ovarian cancer. Oncotarget. 1:210–218. 2010.PubMed/NCBI View Article : Google Scholar
25	Steg AD, Katre AA, Goodman B, Han HD, Nick AM, Stone RL, Coleman RL, Alvarez RD, Lopez-Berestein G, Sood AK, et al: Targeting the notch ligand JAGGED1 in both tumor cells and stroma in ovarian cancer. Clin Cancer Res. 17:5674–5685. 2011.PubMed/NCBI View Article : Google Scholar
26	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
27	Nagini S: Breast Cancer: Current Molecular Therapeutic Targets and New Players. Anticancer Agents Med Chem. 17:152–163. 2017.PubMed/NCBI View Article : Google Scholar
28	Wein L and Loi S: Mechanisms of resistance of chemotherapy in early-stage triple negative breast cancer (TNBC). Breast. 34 (Suppl 1):S27–S30. 2017.PubMed/NCBI View Article : Google Scholar
29	Lehmann BD, Jovanović B, Chen X, Estrada MV, Johnson KN, Shyr Y, Moses HL, Sanders ME and Pietenpol JA: Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLoS One. 11(e0157368)2016.PubMed/NCBI View Article : Google Scholar
30	O'Reilly EA, Gubbins L, Sharma S, Tully R, Guang MH, Weiner-Gorzel K, McCaffrey J, Harrison M, Furlong F, Kell M, et al: The fate of chemoresistance in triple negative breast cancer (TNBC). BBA Clin. 3:257–275. 2015.PubMed/NCBI View Article : Google Scholar
31	Das S: Identification and targeting of microRNAs modulating acquired chemotherapy resistance in Triple negative breast cancer (TNBC): A better strategy to combat chemoresistance. Med Hypotheses. 96:5–8. 2016.PubMed/NCBI View Article : Google Scholar
32	Tang Q, Ouyang H, He D, Yu C and Tang G: MicroRNA-based potential diagnostic, prognostic and therapeutic applications in triple-negative breast cancer. Artif Cells Nanomed Biotechnol. 47:2800–2809. 2019.PubMed/NCBI View Article : Google Scholar
33	Gupta I, Sareyeldin RM, Al-Hashimi I, Al-Thawadi HA, Al Farsi H, Vranic S and Al Moustafa AE: Triple Negative Breast Cancer Profile, from Gene to microRNA, in Relation to Ethnicity. Cancers (Basel). 11(363)2019.PubMed/NCBI View Article : Google Scholar
34	Xing F, Wang S and Zhou J: The Expression of MicroRNA-598 Inhibits Ovarian Cancer Cell Proliferation and Metastasis by Targeting URI. Mol Ther Oncolytics. 12:9–15. 2018.PubMed/NCBI View Article : Google Scholar
35	Wang N, Zhang Y and Liang H: MicroRNA-598 Inhibits Cell Proliferation and Invasion of Glioblastoma by Directly Targeting Metastasis Associated in Colon Cancer-1 (MACC1). Oncol Res. 26:1275–1283. 2018.PubMed/NCBI View Article : Google Scholar
36	Li D, Masiero M, Banham AH and Harris AL: The notch ligand JAGGED1 as a target for anti-tumor therapy. Front Oncol. 4(254)2014.PubMed/NCBI View Article : Google Scholar
37	Liu Z, Zhang G, Yu W, Gao N and Peng J: miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1. Biochem Biophys Res Commun. 469:692–697. 2016.PubMed/NCBI View Article : Google Scholar
38	Tang L, Yang B, Cao X, Li Q, Jiang L and Wang D: MicroRNA-377-3p inhibits growth and invasion through sponging JAG1 in ovarian cancer. Genes Genomics. 41:919–926. 2019.PubMed/NCBI View Article : Google Scholar
39	Duan K, Ge YC, Zhang XP, Wu SY, Feng JS, Chen SL, Zhang LI, Yuan ZH and Fu CH: miR-34a inhibits cell proliferation in prostate cancer by downregulation of SIRT1 expression. Oncol Lett. 10:3223–3227. 2015.PubMed/NCBI View Article : Google Scholar