Upregulation of microRNA-181b inhibits CCL18-induced breast cancer cell metastasis and invasion via the NF-κB signaling pathway Retraction in /10.3892/ol.2024.14401

Wang,Lei; Wang,Yu‑Xia; Chen,Li‑Ping; Ji,Ming‑Li

doi:10.3892/ol.2016.5230

Upregulation of microRNA-181b inhibits CCL18-induced breast cancer cell metastasis and invasion via the NF-κB signaling pathway

Retraction in: /10.3892/ol.2024.14401

Authors:
- Lei Wang
- Yu‑Xia Wang
- Li‑Ping Chen
- Ming‑Li Ji
View Affiliations

Affiliations: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China, Department of Pathophysiology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Department of Physiology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
Published online on: October 5, 2016 https://doi.org/10.3892/ol.2016.5230
Pages: 4411-4418
Copyright: © Wang 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

The purpose of the present study was to investigate the effects of upregulating microRNA (miR)-181b expression in tumor-associated macrophages regarding breast cancer cell metastasis and to identify the target gene. Ectopic miR‑181b was transfected into MDA‑MB‑231 and MCF‑7 breast cancer cell lines with or without chemokine ligand 18 (CCL18) stimulation. Cell proliferation, migration/invasion and apoptosis rate were investigated. The binding effects of miR‑181b to the 3'‑untranslated region (UTR) of the nuclear factor (NF)‑κB gene were detected with the dual luciferase reporter system. Immunofluorescent staining of the NF‑κB key component P65 was performed. The messenger (m) RNA and protein expression of NF‑κB induced by CCL18 with or without miR‑181b stimulation was evaluated with reverse transcription‑quantitative polymerase chain reaction and western blot analysis. When compared with the CCL18‑stimulated group, miR‑181b mimic-transfected cells exhibited significantly inhibited proliferation and migration, with an increased cell apoptosis percentage in a dose‑dependent manner. Furthermore, the luciferase activity was reduced for cells with NF‑κB 3'‑UTR wild‑type that were co‑transfected with miR‑181b mimics. Immunofluorescent staining of NF‑κB demonstrably weakened the P65 signal in stimulated miR‑181b mimic cells when compared with parental and CCL18‑treated cells. The increased expression level of NF‑κB induced by CCL18 in MDA‑MB‑231 and MCF‑7 cells was suppressed by miR‑181b mimics. Overexpression of miR‑181b suppressed cell survival rate and migration. This overexpression may achieve this goal by regulating the NF‑κB pathway in breast cancer cells. Our study demonstrated a potential therapeutic application of miR‑181b in the treatment of breast cancer.

View Figures

View References

1	Condeelis J and Pollard JW: Macrophages: Obligate partners for tumor cell migration, invasion, and metastasis. Cell. 124:263–266. 2006. View Article : Google Scholar : PubMed/NCBI
2	Kolahdooz F, Jang SL, Corriveau A, Gotay C, Johnston N and Sharma S: Knowledge, attitudes, and behaviours towards cancer screening in indigenous populations: A systematic review. Lancet Oncol. 15:e504–e516. 2014. View Article : Google Scholar : PubMed/NCBI
3	Amarilio R, Ramachandran S, Sabanay H and Lev S: Differential regulation of endoplasmic reticulum structure through VAP-Nir protein interaction. J Biol Chem. 280:5934–5944. 2005. View Article : Google Scholar : PubMed/NCBI
4	Chang CY, Lee YH, Leu SJ, Wang CY, Wei CP, Hung KS, Pai MH, Tsai MD and Wu CH: CC-chemokine ligand 18/pulmonary activation-regulated chemokine expression in the CNS with special reference to traumatic brain injuries and neoplastic disorders. Neuroscience. 165:1233–1243. 2010. View Article : Google Scholar : PubMed/NCBI
5	Tang X: Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer. Cancer Lett. 332:3–10. 2013. View Article : Google Scholar : PubMed/NCBI
6	Coussens LM, Tinkle CL, Hanahan D and Werb Z: MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell. 103:481–490. 2000. View Article : Google Scholar : PubMed/NCBI
7	DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N and Coussens LM: CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 16:91–102. 2009. View Article : Google Scholar : PubMed/NCBI
8	Chen J, Yao Y, Gong C, Yu F, Su S, Chen J, Liu B, Deng H, Wang F, Lin L, et al: CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell. 19:541–555. 2011. View Article : Google Scholar : PubMed/NCBI
9	Marino AL, Evangelista AF, Vieira RA, Macedo T, Kerr LM, Abrahão-Machado LF, Longatto-Filho A, Silveira HC and Marques MM: MicroRNA expression as risk biomarker of breast cancer metastasis: A pilot retrospective case-cohort study. BMC Cancer. 14:7392014. View Article : Google Scholar : PubMed/NCBI
10	Kim VN and Nam JW: Genomics of microRNA. Trends Genet. 22:165–173. 2006. View Article : Google Scholar : PubMed/NCBI
11	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
12	Carthew RW and Sontheimer EJ: Origins and mechanisms of miRNAs and siRNAs. Cell. 136:642–655. 2009. View Article : Google Scholar : PubMed/NCBI
13	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
14	Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M and Campiglio M: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65:7065–7070. 2005. View Article : Google Scholar : PubMed/NCBI
15	Sochor M, Basova P, Pesta M, Dusikova P, 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
16	Mansueto G, Forzati F, Ferraro A, Pallante P, Bianco M, Esposito F, Iaccarino A, Troncone G and Fusco A: Identification of a new pathway for tumor progression: MicroRNA-181b up-regulation and CBX7 down-regulation by HMGA1 protein. Genes Cancer. 1:210–224. 2010. View Article : Google Scholar : PubMed/NCBI
17	Liu J, Wu C, Ju J and Jiang J: miR-181b as a key regulator of the oncogenic process and its clinical implications in cancer (Review). Biomed Rep. 2:7–11. 2014.PubMed/NCBI
18	Wang B, Hsu SH, Majumder S, Kutay H, Huang W, Jacob ST and Ghoshal K: TGFbeta-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene. 29:1787–1797. 2010. View Article : Google Scholar : PubMed/NCBI
19	Sun X, Icli B, Wara AK, Belkin N, He S, Kobzik L, Hunninghake GM and Vera MP: MICU Registry, Blackwell TS, et al: MicroRNA-181b regulates NF-κB-mediated vascular inflammation. J Clin Invest. 122:1973–1990. 2012.PubMed/NCBI
20	Shi L, Cheng Z, Zhang J, Li R, Zhao P, Zhao P, Fu Z and You Y: hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res. 1236:185–193. 2008. View Article : Google Scholar : PubMed/NCBI
21	Kroski E, Fiori ME, Barbieri O, Astigiano S, Mirisola V, Killian PH, Bruno A, Pagani A, Rovera F, Pfeffer U, et al: miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down regulation of the inflammatory cytokines CXCL-1 and −2. Mol Oncol. 8:581–595. 2014. View Article : Google Scholar : PubMed/NCBI
22	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
23	Karin M, Cao Y, Greten FR and Li ZW: NF-kappab in cancer: From innocent bystander to major culprit. Nat Rev Cancer. 2:301–310. 2002. View Article : Google Scholar : PubMed/NCBI
24	Slaby O: MicroRNA-181 family predicts response to concomitant chemoradiotherapy with temozolomide in glioblastoma patients. Neoplasma. 57:264–269. 2010. View Article : Google Scholar : PubMed/NCBI
25	Yang J, Liu H, Wang H and Sun Y: Down-regulation of microRNA-181b is a potential prognostic marker of non-small cell lung cancer. Pathol Res Pract. 209:490–494. 2013. View Article : Google Scholar : PubMed/NCBI
26	Visone R, Veronese A, Rassenti LZ, Balatti V, Pearl DK, Acunzo M, Volinia S, Taccioli C, Kipps TJ and Croce CM: miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia. Blood. 118:3072–3079. 2011. View Article : Google Scholar : PubMed/NCBI
27	Xu RX, Liu RY, Wu CM, Zhao YS, Li Y, Yao YQ and Xu YH: DNA damage-induced NF-κB activation in human glioblastoma cells promotes miR-181 bexpression and cell proliferation. Cell Physiol Biochem. 35:913–925. 2015. View Article : Google Scholar : PubMed/NCBI
28	Wang B, Hsu SH, Majumder S, Kutay H, Huang W, Jacob ST and Ghoshal K: TGFbeta-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene. 29:1787–1797. 2010. View Article : Google Scholar : PubMed/NCBI
29	Zehavi L, Schayek H, Jacob-Hirsch J, Sidi Y, Leibowitz-Amit R and Avni D: MiR-377 targets E2F3 and alters the NF-κB signaling pathway through MAP3K7 in malignant melanoma. Mol Cancer. 14:682015. View Article : Google Scholar : PubMed/NCBI
30	Barbie TU, Alexe G, Aref AR, Li S, Zhu Z, Zhang X, Imamura Y, Thai TC, Huang Y, Bowden M, et al: Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth. J Clin Invest. 124:5411–5423. 2014. View Article : Google Scholar : PubMed/NCBI
31	Noma N, Simizu S, Kambayashi Y, Kabe Y, Suematsu M and Umezawa K: Involvement of NF-κB-mediated expression of galectin-3-binding protein in TNF-α-induced breast cancer cell adhesion. Oncol Rep. 27:2080–2084. 2012.PubMed/NCBI
32	Su S, Liu Q, Chen J, Chen J, Chen F, He C, Huang D, Wu W, Lin L, Huang W, et al: A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell. 25:605–620. 2014. View Article : Google Scholar : PubMed/NCBI
33	Pollard JW: Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004:71–78. 2004. View Article : Google Scholar
34	Ma X, Buscaglia LE Becker, Barker JR and Li Y: MicroRNAs in NF-kappaB signaling. J Mol Cell Biol. 3:159–166. 2011. View Article : Google Scholar : PubMed/NCBI
35	Zhu W, Shan X, Wang T, Shu Y and Liu P: miR-181b modulates multidrug resistance by targeting BCL2 in human cancer cell lines. Int J Cancer. 127:2520–2529. 2010. View Article : Google Scholar : PubMed/NCBI
36	Shi L: hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res. 1236:185–193. 2008. View Article : Google Scholar : PubMed/NCBI
37	Squadrito ML, Etzrodt M, De Palma M and Pittet MJ: MicroRNA-mediated control of macrophages and its implications for cancer. Trends Immunol. 34:350–359. 2013. View Article : Google Scholar : PubMed/NCBI
38	Sun X, Icli B, Wara AK, Belkin N, He S, Kobzik L, Huninghake GM and Vera MP: MICU Registry, Blackwell TS, et al: MicroRNA-181b regulates NF-κB-mediated vascular inflammation. J Clin Invest. 122:1973–1990. 2012.PubMed/NCBI
39	Xie WD, Li MN, Xu NH, Lv Q, Huang N, He J and Zhang Y: miR-181a regulates inflammation responses in monocytes and macrophages. PLoS One. 8:e586392013. View Article : Google Scholar : PubMed/NCBI
40	Nariţa D, Seclaman E, Ursoniu S, Ilina R, Cireap N and Anghel A: Expression of CCL18 and interleukin-6 in the plasma of breast cancer patients as compared with benign tumor patients and healthy controls. Rom J Morphol Embryol. 52:1261–1267. 2011.PubMed/NCBI
41	Zhang W, Shen X, Xie L, Chu M and Ma Y: MicroRNA-181b regulates endotoxin tolerance by targeting IL-6 in macrophage RAW264.7 cells. J Inflamm (Lond). 12:182015. View Article : Google Scholar : PubMed/NCBI
42	Jing H and Lee S: NF-κB in cellular senescence and cancer treatment. Mol Cells. 37:189–195. 2014. View Article : Google Scholar : PubMed/NCBI
43	Erstad DJ and Cusack JC Jr: Targeting the NF-κB pathway in cancer therapy. Surg Oncol Clin N Am. 22:705–746. 2013. View Article : Google Scholar : PubMed/NCBI
44	Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML and Struhl K: STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell. 39:493–506. 2010. View Article : Google Scholar : PubMed/NCBI
45	Schetter AJ, Heegaard NH and Harris CC: Inflammation and cancer: Interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis. 31:37–49. 2010. View Article : Google Scholar : PubMed/NCBI
46	Lin X, Chen L, Yao Y, Zhao R, Cui X, Chen J, Hou K, Zhang M, Su F, Chen J and Song E: CCL18-mediated down-regulation of miR98 and miR27b promotes breast cancer metastasis. Oncotarget. 6:20485–20499. 2015. View Article : Google Scholar : PubMed/NCBI