microRNA-146a targets the L1 cell adhesion molecule and suppresses the metastatic potential of gastric cancer

Hou,Zhibo; Yin,Haitao; Chen,Cong; Dai,Xinzheng; Li,Xiaolin; Liu,Baorui; Fang,Xuefeng

doi:10.3892/mmr.2012.946

September 2012 Volume 6 Issue 3

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September 2012 Volume 6 Issue 3

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Article

microRNA-146a targets the L1 cell adhesion molecule and suppresses the metastatic potential of gastric cancer

Authors:
- Zhibo Hou
- Haitao Yin
- Cong Chen
- Xinzheng Dai
- Xiaolin Li
- Baorui Liu
- Xuefeng Fang
View Affiliations / Copyright

Affiliations: Department of Oncology, The Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210029, P.R. China , Department of Gynecology of Traditional Chinese Medicine, Jiangsu Provincial Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China , Department of Liver Surgery, Liver Transplantation Center of Jiangsu Province, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China , Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China , The Comprehensive Cancer Center of Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210008, P.R. China , Department of Medical Oncology, Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, P.R. China
Pages: 501-506
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Published online on: June 13, 2012

https://doi.org/10.3892/mmr.2012.946
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Abstract

Recent studies have shown that microRNA-146a (miR-146a) is associated with cancer metastasis. However, the mechanisms underlying this process remain poorly understood. In this study, we aimed to investigate the potential role of miR-146a in gastric cancer metastasis. A wound-healing assay and a Transwell assay were used to investigate the impact of miR-146a on the migratory and invasive abilities of MKN-45 cells in vitro. MKN-45 cells stably expressing miR-146a or the negative control were transplanted into nude mice through the lateral tail vein to explore the effect of miR-146a on tumor metastasis in vivo. A luciferase reporter assay and western blot analysis were used to identify the potential target genes. Our results show that the overexpression of miR-146a inhibits the invasion and metastasis of MKN-45 cells in vitro and in vivo. Furthermore, the L1 cell adhesion molecule (L1CAM) was identified as a novel target of miR‑146a in gastric cancer. Taken together, our results provide evidence that miR-146a suppresses gastric cancer cell invasion and metastasis in vitro and in vivo, which may be in part due to the downregulation of L1CAM. miR-146a may have the therapeutic potential to suppress gastric cancer metastasis.

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1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
2	Leung WK, Wu MS, Kakugawa Y, et al: Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 9:279–287. 2008. View Article : Google Scholar : PubMed/NCBI
3	Yang L: Incidence and mortality of gastric cancer in China. World J Gastroenterol. 12:17–20. 2006.
4	Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J and Benz CC: Expression of microRNA-146 suppresses NF-κB activity with reduction of metastatic potential in breast cancer cells. Oncogene. 27:5643–5647. 2008.PubMed/NCBI
5	Nicoloso MS, Spizzo R, Shimizu M, Rossi S and Calin GA: MicroRNAs - the micro steering wheel of tumour metastases. Nat Rev Cancer. 9:293–302. 2009. View Article : Google Scholar : PubMed/NCBI
6	Wang X, Tang S, Le SY, et al: Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One. 3:e25572008. View Article : Google Scholar : PubMed/NCBI
7	Lin SL, Chiang A, Chang D and Ying SY: Loss of mir-146a function in hormone-refractory prostate cancer. RNA. 14:417–424. 2008. View Article : Google Scholar : PubMed/NCBI
8	Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR and de la Chapelle A: Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA. 105:7269–7274. 2008. View Article : Google Scholar : PubMed/NCBI
9	Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS and Welch DR: Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res. 69:1279–1283. 2009. View Article : Google Scholar : PubMed/NCBI
10	Mei J, Bachoo R and Zhang CL: MicroRNA-146a inhibits glioma development by targeting Notch1. Mol Cell Biol. 31:3584–3592. 2011. View Article : Google Scholar : PubMed/NCBI
11	Paik JH, Jang JY, Jeon YK, et al: MicroRNA-146a downregulates NFκB activity via targeting TRAF6 and functions as a tumor suppressor having strong prognostic implications in NK/T cell lymphoma. Clin Cancer Res. 17:4761–4771. 2011.PubMed/NCBI
12	Li Y, Vandenboom TG 2nd, Wang Z, et al: miR-146a suppresses invasion of pancreatic cancer cells. Cancer Res. 70:1486–1495. 2010. View Article : Google Scholar : PubMed/NCBI
13	Pacifico F, Crescenzi E, Mellone S, et al: Nuclear factor-κB contributes to anaplastic thyroid carcinomas through up-regulation of miR-146a. J Clin Endocrinol Metab. 95:1421–1430. 2010.
14	Hou Z, Xie L, Yu L, Qian X and Liu B: MicroRNA-146a is down-regulated in gastric cancer and regulates cell proliferation and apoptosis. Med Oncol. 29:886–892. 2012. View Article : Google Scholar : PubMed/NCBI
15	Kogo R, Mimori K, Tanaka F, Komune S and Mori M: Clinical significance of miR-146a in gastric cancer cases. Clin Cancer Res. 17:4277–4284. 2011. View Article : Google Scholar : PubMed/NCBI
16	Tchernitsa O, Kasajima A, Schafer R, et al: Systematic evaluation of the miRNA-ome and its downstream effects on mRNA expression identifies gastric cancer progression. J Pathol. 222:310–319. 2010. View Article : Google Scholar : PubMed/NCBI
17	Liang CC, Park AY and Guan JL: In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2:329–333. 2007. View Article : Google Scholar : PubMed/NCBI
18	Raveh S, Gavert N and Ben-Ze’ev A: L1 cell adhesion molecule (L1CAM) in invasive tumors. Cancer Lett. 282:137–145. 2009. View Article : Google Scholar : PubMed/NCBI
19	Kodera Y, Nakanishi H, Ito S, et al: Expression of L1 cell adhesion molecule is a significant prognostic factor in pT3-stage gastric cancer. Anticancer Res. 29:4033–4039. 2009.PubMed/NCBI
20	Xiao B, Zhu ED, Li N, et al: Increased miR-146a in gastric cancer directly targets SMAD4 and is involved in modulating cell proliferation and apoptosis. Oncol Rep. 27:559–566. 2012.PubMed/NCBI
21	Rathjen FG and Schachner M: Immunocytological and biochemical characterization of a new neuronal cell surface component (L1 antigen) which is involved in cell adhesion. EMBO J. 3:1–10. 1984.PubMed/NCBI
22	Gavert N, Conacci-Sorrell M, Gast D, et al: L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol. 168:633–642. 2005. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

microRNA-146a targets the L1 cell adhesion molecule and suppresses the metastatic potential of gastric cancer

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