MicroRNA‑181 serves an oncogenic role in breast cancer via the inhibition of SPRY4 Retraction in /10.3892/mmr.2022.12673

Tian,Yifu; Fu,Xiaodan; Li,Qingling; Wang,Ying; Fan,Dan; Zhou,Qin; Kuang,Weilu; Shen,Liangfang

doi:10.3892/mmr.2018.9572

MicroRNA‑181 serves an oncogenic role in breast cancer via the inhibition of SPRY4

Retraction in: /10.3892/mmr.2022.12673

Authors:
- Yifu Tian
- Xiaodan Fu
- Qingling Li
- Ying Wang
- Dan Fan
- Qin Zhou
- Weilu Kuang
- Liangfang Shen
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Affiliations: Department of Pathology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China, Department of Oncology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
Published online on: October 22, 2018 https://doi.org/10.3892/mmr.2018.9572
Pages: 5603-5613
Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Numerous microRNAs (miRs) have been implicated in breast cancer; however, the molecular mechanism is not fully understood. The present study examined the function and regulatory mechanism of miR‑181 in breast cancer. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to examine the RNA and protein expression. MTT assay, wound healing assay and transwell assay were conducted to study cell proliferation, migration and invasion. Luciferase reporter gene assay was used to confirm targeting relationship. The results suggested that the miR‑181 expression levels were significantly higher in breast cancer cell lines and clinical tissue samples. The increased expression of miR‑181 was markedly associated with higher clinical stage and lymph node metastasis. The patients with high miR‑181 expression demonstrated worse prognosis compared with those with a low expression of miR‑181. Small interfering RNA‑induced miR‑181 downregulation significantly inhibited breast cancer cell proliferation, migration and invasion in vitro, and tumor growth in vivo. Protein sprouty homolog 4 (SPRY4), downregulated in breast cancer tissues and cell lines, was observed to be a novel target gene of miR‑181. Downregulation of SPRY4 was significantly associated with breast cancer progression in addition to poor prognosis. Knockdown of SPRY4 rescued the inhibitory effects of miR‑181 downregulation on the malignant phenotypes of breast cancer cells. Thus, the present study demonstrated that miR‑181 serves a promoting role in breast cancer at least in part through the inhibition of SPRY4 expression. The present results expand the understanding of the miR‑181/SPRY4 axis' function during for the malignant progression of breast cancer.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Shao P, Liu Q, Maina PK, Cui J, Bair TB, Li T, Umesalma S, Zhang W and Qi HH: Histone demethylase PHF8 promotes epithelial to mesenchymal transition and breast tumorigenesis. Nucleic Acids Res. 45:1687–1702. 2017. View Article : Google Scholar : PubMed/NCBI
3	Liu R, Shi P, Nie Z, Liang H, Zhou Z, Chen W, Chen H, Dong C, Yang R, Liu S and Chen C: Mifepristone suppresses basal triple-negative breast cancer stem cells by down-regulating KLF5 expression. Theranostics. 6:533–544. 2016. View Article : Google Scholar : PubMed/NCBI
4	Koufaris C, Valbuena GN, Pomyen Y, Tredwell GD, Nevedomskaya E, Lau CH, Yang T, Benito A, Ellis JK and Keun HC: Systematic integration of molecular profiles identifies miR-22 as a regulator of lipid and folate metabolism in breast cancer cells. Oncogene. 35:2766–2776. 2016. View Article : Google Scholar : PubMed/NCBI
5	Zhou Y, Yang C, Wang K, Liu X and Liu Q: MicroRNA-33b inhibits the proliferation and migration of osteosarcoma cells via targeting hypoxia-inducible factor-1α. Oncol Res. 25:397–405. 2017. View Article : Google Scholar : PubMed/NCBI
6	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
7	Croce CM and Calin GA: miRNAs, cancer, and stem cell division. Cell. 122:6–7. 2005. View Article : Google Scholar : PubMed/NCBI
8	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
9	Zhu H, Huang L, Zhu S, Li X, Li Z, Yu C and Yu X: Regulation of autophagy by systemic admission of microRNA-141 to target HMGB1 in l-arginine-induced acute pancreatitis in vivo. Pancreatology. 16:337–346. 2016. View Article : Google Scholar : PubMed/NCBI
10	Trümbach D and Prakash N: The conserved miR-8/miR-200 microRNA family and their role in invertebrate and vertebrate neurogenesis. Cell Tissue Res. 359:161–177. 2015. View Article : Google Scholar : PubMed/NCBI
11	Wu X, Li L, Li Y and Liu Z: MiR-153 promotes breast cancer cell apoptosis by targeting HECTD3. Am J Cancer Res. 6:1563–1571. 2016.PubMed/NCBI
12	Wang DS, Zhang HQ, Zhang B, Yuan ZB, Yu ZK, Yang T, Zhang SQ, Liu Y and Jia XX: miR-133 inhibits pituitary tumor cell migration and invasion via down-regulating FOXC1 expression. Genet Mol Res. 15:2016.(doi: 10.4238/gmr.15017453).
13	Li X, Li Y and Lu H: MiR-1193 suppresses proliferation and invasion of human breast cancer cells through directly targeting IGF2BP2. Oncol Res. 25:579–585. 2017. View Article : Google Scholar : PubMed/NCBI
14	Ye ZB, Ma G, Zhao YH, Xiao Y, Zhan Y, Jing C, Gao K, Liu ZH and Yu SJ: miR-429 inhibits migration and invasion of breast cancer cells in vitro. Int J Oncol. 46:531–538. 2015. View Article : Google Scholar : PubMed/NCBI
15	Liu Y, Hu X, Xia D and Zhang S: MicroRNA-181b is downregulated in non-small cell lung cancer and inhibits cell motility by directly targeting HMGB1. Oncol Lett. 12:4181–4186. 2016. View Article : Google Scholar : PubMed/NCBI
16	Zhi F, Wang Q, Deng D, Shao N, Wang R, Xue L, Wang S, Xia X and Yang Y: MiR-181b-5p downregulates NOVA1 to suppress proliferation, migration and invasion and promote apoptosis in astrocytoma. PLoS One. 9:e1091242014. View Article : Google Scholar : PubMed/NCBI
17	Bisso A, Faleschini M, Zampa F, Capaci V, De Santa J, Santarpia L, Piazza S, Cappelletti V, Daidone M, Agami R and Del Sal G: Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer. Cell Cycle. 12:1679–1687. 2013. View Article : Google Scholar : PubMed/NCBI
18	Yoo JO, Kwak SY, An HJ, Bae IH, Park MJ and Han YH: miR-181b-3p promotes epithelial-mesenchymal transition in breast cancer cells through Snail stabilization by directly targeting YWHAG. Biochim Biophys Acta. 1863:1601–1611. 2016. View Article : Google Scholar : PubMed/NCBI
19	Zheng Y, Lv X, Wang X, Wang B, Shao X, Huang Y, Shi L, Chen Z, Huang J and Huang P: MiR-181b promotes chemoresistance in breast cancer by regulating Bim expression. Oncol Rep. 35:683–690. 2016. View Article : Google Scholar : PubMed/NCBI
20	Taylor MA, Sossey-Alaoui K, Thompson CL, Danielpour D and Schiemann WP: TGF-β upregulates miR-181a expression to promote breast cancer metastasis. J Clin Invest. 123:150–163. 2013. View Article : Google Scholar : PubMed/NCBI
21	Niu J, Xue A, Chi Y, Xue J, Wang W, Zhao Z, Fan M, Yang CH, Shao ZM, Pfeffer LM, et al: Induction of miRNA-181a by genotoxic treatments promotes chemotherapeutic resistance and metastasis in breast cancer. Oncogene. 35:1302–1313. 2016. View Article : Google Scholar : PubMed/NCBI
22	Neel JC and Lebrun JJ: Activin and TGFβ regulate expression of the microRNA-181 family to promote cell migration and invasion in breast cancer cells. Cell Signal. 25:1556–1566. 2013. View Article : Google Scholar : PubMed/NCBI
23	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
24	Sochor M, Basova P, Pesta M, Dusilkova N, Bartos J, Burda P, Pospisil V and Stopka T: Oncogenic microRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum. BMC Cancer. 14:4482014. View Article : Google Scholar : PubMed/NCBI
25	Li M, Zhang H, Zhao X, Yan L, Wang C and Li C and Li C: SPRY4-mediated ERK1/2 signaling inhibition abolishes 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell. Gynecol Endocrinol. 30:600–604. 2014. View Article : Google Scholar : PubMed/NCBI
26	Sun M, Huang F, Yu D, Zhang Y, Xu H, Zhang L, Li L, Dong L, Guo L and Wang S: Autoregulatory loop between TGF-β1/miR-411-5p/SPRY4 and MAPK pathway in rhabdomyosarcoma modulates proliferation and differentiation. Cell Death Dis. 6:e18592015. View Article : Google Scholar : PubMed/NCBI
27	Zhou X, Xie S, Yuan C, Jiang L, Huang X, Li L, Chen Y, Luo L, Zhang J, Wang D, et al: Lower expression of SPRY4 predicts a poor prognosis and regulates cell proliferation in colorectal cancer. Cell Physiol Biochem. 40:1433–1442. 2016. View Article : Google Scholar : PubMed/NCBI
28	Vanas V, Mühlbacher E, Kral R and Sutterlüty-Fall H: Sprouty4 interferes with cell proliferation and migration of breast cancer-derived cell lines. Tumour Biol. 35:4447–4456. 2014. View Article : Google Scholar : PubMed/NCBI
29	Jing H, Liaw L, Friesel R, Vary C, Hua S and Yang X: Suppression of Spry4 enhances cancer stem cell properties of human MDA-MB-231 breast carcinoma cells. Cancer Cell Int. 16:192016. View Article : Google Scholar : PubMed/NCBI