miR-198 functions as a tumor suppressor in breast cancer by targeting CUB domain-containing protein 1

Hu,Yingbin; Tang,Ziyuan; Jiang,Bonian; Chen,Juying; Fu,Zhongpin

doi:10.3892/ol.2017.5673

miR-198 functions as a tumor suppressor in breast cancer by targeting CUB domain-containing protein 1

Authors:
- Yingbin Hu
- Ziyuan Tang
- Bonian Jiang
- Juying Chen
- Zhongpin Fu
View Affiliations

Affiliations: Department of Colorectal Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: February 2, 2017 https://doi.org/10.3892/ol.2017.5673
Pages: 1753-1760

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 molecular mechanisms underlying the dysregulation of microRNAs (miRs) have been previously documented in breast cancer. miR-198 has been reported to be deregulated in several human cancers. However, the detailed effects of miR-198 on breast cancer progression remain unclear. Using quantitative polymerase chain reaction analysis, we demonstrated in the present study that miR‑198 was downregulated in breast cancer tissues and cell lines, and that downregulation of miR‑198 was significantly correlated with lymph node metastasis. Functional studies revealed that miR‑198 inhibited cell proliferation and migration and promoted cell adhesion in aggressive breast cancer cells in vitro. In addition, we observed that CUB domain‑containing protein 1 (CDCP1) was a direct target of miR‑198, and that knockdown of CDCP1 inhibited cell proliferation and migration, and promoted cell adhesion, which was similar to the effects of overexpression of miR‑198. Taken together, we provide evidence to characterize the role of miR‑198/CDCP1 interaction in breast cancer, which may be useful in breast cancer therapy.

View Figures

View References

1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
3	Sayed D and Abdellatif M: MicroRNAs in development and disease. Physiol Rev. 91:827–887. 2011. View Article : Google Scholar : PubMed/NCBI
4	Wang M, Wang J, Kong X, Chen H, Wang Y, Qin M, Lin Y, Chen H, Xu J, Hong J, et al: miR-198 represses tumor growth and metastasis in colorectal cancer by targeting fucosyl transferase 8. Sci Rep. 4:61452014. View Article : Google Scholar : PubMed/NCBI
5	Yang J, Zhao H, Xin Y and Fan L: MicroRNA-198 inhibits proliferation and induces apoptosis of lung cancer cells via targeting FGFR1. J Cell Biochem. 115:987–995. 2014. View Article : Google Scholar : PubMed/NCBI
6	Marin-Muller C, Li D, Bharadwaj U, Li M, Chen C, Hodges SE, Fisher WE, Mo Q, Hung MC and Yao Q: A tumorigenic factor interactome connected through tumor suppressor microRNA-198 in human pancreatic cancer. Clin Cancer Res. 19:5901–5913. 2013. View Article : Google Scholar : PubMed/NCBI
7	Vychytilova-Faltejskova P, Kiss I, Klusova S, Klusova S, Hlavsa J, Prochazka V, Kala Z, Mazanec J, Hausnerova J, Kren L, et al: MiR-21, miR-34a, miR-198 and miR-217 as diagnostic and prognostic biomarkers for chronic pancreatitis and pancreatic ductal adenocarcinoma. Diagn Pathol. 10:382015. View Article : Google Scholar : PubMed/NCBI
8	Elfimova N, Sievers E, Eischeid H, Kwiecinski M, Noetel A, Hunt H, Becker D, Frommolt P, Quasdorff M, Steffen HM, et al: Control of mitogenic and motogenic pathways by miR-198, diminishing hepatoma cell growth and migration. Biochim Biophys Acta. 1833:1190–1198. 2013. View Article : Google Scholar : PubMed/NCBI
9	Tan S, Li R, Ding K, Lobie PE and Zhu T: miR-198 inhibits migration and invasion of hepatocellular carcinoma cells by targeting the HGF/c-MET pathway. FEBS Lett. 585:2229–2234. 2011. View Article : Google Scholar : PubMed/NCBI
10	Walter BA, Valera VA, Pinto PA and Merino MJ: Comprehensive microRNA profiling of prostate cancer. J Cancer. 4:350–357. 2013. View Article : Google Scholar : PubMed/NCBI
11	Qi B, Yao WJ, Zhao BS, Qin XG, Wang Y, Wang WJ, Wang TY, Liu SG and Li HC: Involvement of microRNA-198 overexpression in the poor prognosis of esophageal cancer. Asian Pac J Cancer Prev. 14:5073–5076. 2013. View Article : Google Scholar : PubMed/NCBI
12	Awakura Y, Nakamura E, Takahashi T, Kotani H, Mikami Y, Kadowaki T, Myoumoto A, Akiyama H, Ito N, Kamoto T, et al: Microarray-based identification of CUB-domain containing protein 1 as a potential prognostic marker in conventional renal cell carcinoma. J Cancer Res Clin Oncol. 134:1363–1369. 2008. View Article : Google Scholar : PubMed/NCBI
13	Hooper JD, Zijlstra A, Aimes RT, Liang H, Claassen GF, Tarin D, Testa JE and Quigley JP: Subtractive immunization using highly metastatic human tumor cells identifies SIMA135/CDCP1, a 135 kDa cell surface phosphorylated glycoprotein antigen. Oncogene. 22:1783–1794. 2003. View Article : Google Scholar : PubMed/NCBI
14	Ikeda J, Oda T, Inoue M, Uekita T, Sakai R, Okumura M, Aozasa K and Morii E: Expression of CUB domain containing protein (CDCP1) is correlated with prognosis and survival of patients with adenocarcinoma of lung. Cancer Sci. 100:429–433. 2009. View Article : Google Scholar : PubMed/NCBI
15	Liu H, Ong SE, Badu-Nkansah K, Schindler J, White FM and Hynes RO: CUB-domain-containing protein 1 (CDCP1) activates Src to promote melanoma metastasis. Proc Natl Acad Sci USA. 108:1379–1384. 2011. View Article : Google Scholar : PubMed/NCBI
16	Miyazawa Y, Uekita T, Hiraoka N, Fujii S, Kosuge T, Kanai Y, Nojima Y and Sakai R: CUB domain-containing protein 1, a prognostic factor for human pancreatic cancers, promotes cell migration and extracellular matrix degradation. Cancer Res. 70:5136–5146. 2010. View Article : Google Scholar : PubMed/NCBI
17	Uekita T and Sakai R: Roles of CUB domain-containing protein 1 signaling in cancer invasion and metastasis. Cancer Sci. 102:1943–1948. 2011. View Article : Google Scholar : PubMed/NCBI
18	Benes CH, Wu N, Elia AE, Dharia T, Cantley LC and Soltoff SP: The C2 domain of PKCdelta is a phosphotyrosine binding domain. Cell. 121:271–280. 2005. View Article : Google Scholar : PubMed/NCBI
19	Uekita T, Jia L, Narisawa-Saito M, Yokota J, Kiyono T and Sakai R: CUB domain-containing protein 1 is a novel regulator of anoikis resistance in lung adenocarcinoma. Mol Cell Biol. 27:7649–7660. 2007. View Article : Google Scholar : PubMed/NCBI
20	Ikeda JI, Morii E, Kimura H, Tomita Y, Takakuwa T, Hasegawa JI, Kim YK, Miyoshi Y, Noguchi S, Nishida T and Aozasa K: Epigenetic regulation of the expression of the novel stem cell marker CDCP1 in cancer cells. J Pathol. 210:75–84. 2006. View Article : Google Scholar : PubMed/NCBI
21	Seidel J, Kunc K, Possinger K, Jehn C and Lüftner D: Effect of the tyrosine kinase inhibitor lapatinib on CUB-domain containing protein (CDCP1)-mediated breast cancer cell survival and migration. Biochem Biophys Res Commun. 414:226–232. 2011. View Article : Google Scholar : PubMed/NCBI
22	Cermak T, Doyle EL, Christian M, Wang L, Zhang Y, Schmidt C, Baller JA, Somia NV, Bogdanove AJ and Voytas DF: Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res. 39:e822011. View Article : Google Scholar : PubMed/NCBI
23	Garzon R, Marcucci G and Croce CM: Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 9:775–789. 2010. View Article : Google Scholar : PubMed/NCBI
24	Sundaram GM, Common JE, Gopal FE, Srikanta S, Lakshman K, Lunny DP, Lim TC, Tanavde V, Lane EB and Sampath P: ‘See-saw’ expression of microRNA-198 and FSTL1 from a single transcript in wound healing. Nature. 495:103–106. 2013. View Article : Google Scholar : PubMed/NCBI
25	Uekita T, Tanaka M, Takigahira M, Miyazawa Y, Nakanishi Y, Kanai Y, Yanagihara K and Sakai R: CUB-domain-containing protein 1 regulates peritoneal dissemination of gastric scirrhous carcinoma. Am J Pathol. 172:1729–1739. 2008. View Article : Google Scholar : PubMed/NCBI
26	Emerling BM, Benes CH, Poulogiannis G, Bell EL, Courtney K, Liu H, Choo-Wing R, Bellinger G, Tsukazawa KS, Brown V, et al: Identification of CDCP1 as a hypoxia-inducible factor 2α (HIF-2α) target gene that is associated with survival in clear cell renal cell carcinoma patients. Proc Natl Acad Sci USA. 110:3483–3488. 2013. View Article : Google Scholar : PubMed/NCBI
27	Kollmorgen G, Niederfellner G, Lifke A, Spohn GJ, Rieder N, Harring SV, Bauss F, Burtscher H, Lammers R and Bossenmaier B: Antibody mediated CDCP1 degradation as mode of action for cancer targeted therapy. Mol Oncol. 7:1142–1151. 2013. View Article : Google Scholar : PubMed/NCBI