miR‑425‑5p is associated with poor prognosis in patients with breast cancer and promotes cancer cell progression by targeting PTEN

Xiao,Sheng; Zhu,Hongjia; Luo,Jian; Wu,Zhenru; Xie,Mingjun

doi:10.3892/or.2019.7371

miR‑425‑5p is associated with poor prognosis in patients with breast cancer and promotes cancer cell progression by targeting PTEN

Authors:
- Sheng Xiao
- Hongjia Zhu
- Jian Luo
- Zhenru Wu
- Mingjun Xie
View Affiliations

Affiliations: School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Laboratory of Pathology, West China Hospital, Chengdu, Sichuan 610041, P.R. China
Published online on: October 14, 2019 https://doi.org/10.3892/or.2019.7371
Pages: 2550-2560
Copyright: © Xiao 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

Breast cancer (BC) is the most common invasive cancer in women, and it imposes a heavy burden on patients. microRNAs (miRNAs/miRs) have been found to play an important role in the development of tumors, but their role in the malignant progression of BC is unclear. In the present study, the expression level of miR‑425‑5p was examined in patients with BC, and its association with prognosis was investigated. In vitro experiments were performed to examine role of miR‑425‑5p in the development of BC cells. A downstream target gene of miR‑425‑5p was predicted using a miRNA target prediction tool and validated with a luciferase reporter assay. It was found that miR‑425‑5p expression was increased in BC tissues and cell lines, and was associated with tumor size, clinical stage, lymph node metastasis, distant metastasis and poor overall survival in patients with BC. Knockdown of miR‑425‑5p in BC cell lines inhibited proliferation and migration. PTEN was identified as a downstream target gene of miR‑425‑5p. Overexpression of PTEN was demonstrated to partially inhibit the promotional effect of miR‑425‑5p on cell proliferation and migration. Taken together, miR‑425‑5p is associated with poor prognosis, and promotes cell proliferation and migration via PTEN. Thus, miR‑425‑5p may serve as a therapeutic and prognostic marker for BC.

View Figures

View References

1	Davidson NE, Armstrong SA, Coussens LM, Cruz-Correa MR, DeBerardinis RJ, Doroshow JH, Foti M, Hwu P, Kensler TW, Morrow M, et al: AACR cancer progress report 2016. Clin Cancer Res. 22 (Suppl 19):S1–S137. 2016. View Article : Google Scholar : PubMed/NCBI
2	McGuire A, Brown JA, Malone C, McLaughlin R and Kerin MJ: Effects of age on the detection and management of breast cancer. Cancers (Basel). 7:908–929. 2015. View Article : Google Scholar : PubMed/NCBI
3	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
4	Christenson JL, Butterfield KT, Spoelstra NS, Norris JD, Josan JS, Pollock JA, McDonnell DP, Katzenellenbogen BS, Katzenellenbogen JA and Richer JK: MMTV-PyMT and derived Met-1 mouse mammary tumor cells as models for studying the role of the androgen receptor in triple-negative breast cancer progression. Horm Cancer. 8:69–77. 2017. View Article : Google Scholar : PubMed/NCBI
5	Gu G, Dustin D and Fuqua SA: Targeted therapy for breast cancer and molecular mechanisms of resistance to treatment. Curr Opin Pharmacol. 31:97–103. 2016. View Article : Google Scholar : PubMed/NCBI
6	Riobo-Del Galdo NA, Lara Montero Á and Wertheimer EV: Role of hedgehog signaling in breast cancer: Pathogenesis and therapeutic. Cells. 8:E3752019. View Article : Google Scholar : PubMed/NCBI
7	Harbeck N and Gnant M: Breast cancer. Lancet. 389:1134–1150. 2017. View Article : Google Scholar : PubMed/NCBI
8	Wu H, Zhang W, Wu Z, Liu Y, Shi Y, Gong J, Shen W and Liu C: miR-29c-3p regulates DNMT3B and LATS1 methylation to inhibit tumor progression in hepatocellular carcinoma. Cell Death Dis. 10:482019. View Article : Google Scholar : PubMed/NCBI
9	Du H, Xu Q, Xiao S, Wu Z, Gong J, Liu C, Ren G and Wu H: MicroRNA-424-5p acts as a potential biomarker and inhibits proliferation and invasion in hepatocellular carcinoma by targeting TRIM29. Life Sci. 224:1–11. 2019. View Article : Google Scholar : PubMed/NCBI
10	Hausser J and Zavolan M: Identification and consequences of miRNA-target interactions-beyond repression of gene expression. Nat Rev Genet. 15:599–612. 2014. View Article : Google Scholar : PubMed/NCBI
11	Cohen A, Burgos-Aceves MA and Smith Y: Estrogen repression of microRNA as a potential cause of cancer. Biomed Pharmacother. 78:234–238. 2016. View Article : Google Scholar : PubMed/NCBI
12	Bartel DP: Metazoan microRNAs. Cell. 173:20–51. 2018. View Article : Google Scholar : PubMed/NCBI
13	Hobert O: Gene regulation by transcription factors and microRNAs. Science. 319:1785–1786. 2008. View Article : Google Scholar : PubMed/NCBI
14	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
15	Quan J, Li Y, Pan X, Lai Y, He T, Lin C, Zhou L, Zhao L, Sun S, Ding Y, et al: Oncogenic miR-425-5p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma. Oncol Lett. 16:2175–2184. 2018.PubMed/NCBI
16	Zhang JY, Su XP, Li YN and Guo YH: MicroRNA-425-5p promotes the development of prostate cancer via targeting forkhead box J3. Eur Rev Med Pharmacol Sci. 23:547–554. 2019.PubMed/NCBI
17	Jiang C, Cao S, Li N, Jiang L and Sun T: PD-1 and PD-L1 correlated gene expression profiles and their association with clinical outcomes of breast cancer. Cancer Cell Int. 19:2332019. View Article : Google Scholar : PubMed/NCBI
18	Jiang Y, Liu Y, Tan X, Yu S and Luo J: TPX2 as a novel prognostic indicator and promising therapeutic target in triple-negative breast cancer. Clin Breast Cancer. S1526–S8209. Jun 13–2019.(Epub ahead of print).
19	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. View Article : Google Scholar : PubMed/NCBI
20	Turashvili G and Brogi E: Tumor heterogeneity in breast cancer. Front Med. 4:2272017. View Article : Google Scholar
21	Hu L, Gao Y, Cao Y, Zhang Y, Xu M, Wang Y, Jing Y, Guo S, Jing F, Hu X and Zhu Z: Identification of arginine and its ‘downstream’ molecules as potential markers of breast cancer. IUBMB Life. 68:817–822. 2016. View Article : Google Scholar : PubMed/NCBI
22	Cao S, Zheng J, Liu X, Liu Y, Ruan X, Ma J, Liu L, Wang D, Yang C, Cai H, et al: FXR1 promotes the malignant biological behavior of glioma cells via stabilizing MIR17HG. J Exp Clin Cancer Res. 38:372019. View Article : Google Scholar : PubMed/NCBI
23	Zhang Y, Hu X, Miao X, Zhu K, Cui S, Meng Q, Sun J and Wang T: MicroRNA-425-5p regulates chemoresistance in colorectal cancer cells via regulation of programmed cell death 10. J Cell Mol Med. 20:360–369. 2016. View Article : Google Scholar : PubMed/NCBI
24	Yang G, Zhang C, Wang N and Chen J: miR-425-5p decreases LncRNA MALAT1 and TUG1 expressions and suppresses tumorigenesis in osteosarcoma via Wnt/β-catenin signaling pathway. Int J Biochem Cell Biol. 111:42–51. 2019. View Article : Google Scholar : PubMed/NCBI
25	Charzewska A, Rzońca S, Janeczko M, Nawara M, Smyk M, Bal J and Hoffman-Zacharska D: A duplication of the whole KIAA2022 gene validates the gene role in the pathogenesis of intellectual disability and autism. Clin Genet. 88:297–299. 2015. View Article : Google Scholar : PubMed/NCBI
26	Melchior B, Mittapalli GK, Lai C, Duong-Polk K, Stewart J, Güner B, Hofilena B, Tjitro A, Anderson SD, Herman DS, et al: Tau pathology reduction with SM07883, a novel, potent, and selective oral DYRK1A inhibitor: A potential therapeutic for Alzheimer's disease. Aging Cell. 18:e130002019. View Article : Google Scholar : PubMed/NCBI
27	Wu J and Chen H, Ye M, Wang B, Zhang Y, Sheng J, Meng T and Chen H: Downregulation of long noncoding RNA HCP5 contributes to cisplatin resistance in human triple-negative breast cancer via regulation of PTEN expression. Biomed Pharmacother. 115:1088692019. View Article : Google Scholar : PubMed/NCBI
28	Zhu L, Wang X, Wang T, Zhu W and Zhou X: miR-494-3p promotes the progression of endometrial cancer by regulating the PTEN/PI3K/AKT pathway. Mol Med Rep. 19:581–588. 2019.PubMed/NCBI
29	Shen F, Zheng H, Zhou L, Li W, Liu J and Xu X: Identification of CD28 and PTEN as novel prognostic markers for cervical cancer. J Cell Physiol. 234:7004–7011. 2019. View Article : Google Scholar : PubMed/NCBI
30	Liang L, Williams MD and Bell D: Expression of PTEN, androgen receptor, HER2/neu, cytokeratin 5/6, estrogen receptor-beta, HMGA2, and PLAG1 in salivary duct carcinoma. Head Neck Pathol. Nov 2–2018.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
31	Zhu L, Zhang C and Liu Q: PTEN S-nitrosylation by NOS1 inhibits autophagy in NPC cells. Cell Death Dis. 10:3062019. View Article : Google Scholar : PubMed/NCBI
32	Zhao C, Tao T, Yang L, Qin Q, Wang Y, Liu H, Song R, Yang X, Wang Q, Gu S, et al: Loss of PDZK1 expression activates PI3K/AKT signaling via PTEN phosphorylation in gastric cancer. Cancer Lett. 453:107–121. 2019. View Article : Google Scholar : PubMed/NCBI
33	Cui C, Li S and Wu D: Znhit1 inhibits breast cancer by up-regulating PTEN to deactivate the PI3K/Akt/mTOR pathway. Life Sci. 224:204–211. 2019. View Article : Google Scholar : PubMed/NCBI