miR-22 is down-regulated in esophageal squamous cell carcinoma and inhibits cell migration and invasion

Cancer Cell International

Wei Xu²  Xiaomin Qin¹  Zhaoyuan Li¹  Siqing Ning¹  Chao Yang¹ 

[1] Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441000, China;Department of Dermatology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, 136 Jingzhou Street, Xiangyang 441000, China

关键词: Migration;    Invasion;    Esophageal squamous cell carcinoma;    miR-22;   

Others  :  1121609
DOI  :  10.1186/s12935-014-0138-0

 received in 2014-10-08, accepted in 2014-11-22,  发布年份 2014

【 摘 要 】

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly forms of cancer. Despite advances in the diagnosis and treatment of this cancer, the survival rate at five years is poor. Lately, miR-22 is identified as a tumor-suppressing microRNA in many human cancers. However, the specific function of miR-22 in ESCC is unclear at this point.

Methods

We first measured miR-22 expression level in 30 paired of ESCC and matched normal tissues, ESCC cell lines by real-time quantitative RT-PCR. Invasion assay, MTT proliferation assay and wound-healing assay were performed to test the invasion and proliferation of ESCC cell after overexpression of miR-22.

Results

We found that the expression of miR-22 in ESCC tissues and cell lines were much lower than that in normal control, respectively. The expression of miR-22 was inversely correlated with ESCC metastatic ability. Furthermore, transfection of miR-22 expression plasmid could significantly inhibit the cell proliferation, migration and invasion in Eca109 and Kyse410 ESCC cell lines.

Conclusions

Our findings suggest that miR-22 act as tumor suppressor and inhibiting ESCC cell migration and invasion. The findings of this study contribute to the current understanding of the functions of miR-22 in ESCC.

【 授权许可】

   
2014 Yang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Matsushima K, Isomoto H, Kohno S, Nakao K: MicroRNAs and esophageal squamous cell carcinoma. Digestion 2010, 82(3):138-144.
• [2]Mathe EA, Nguyen GH, Bowman ED, Zhao Y, Budhu A, Schetter AJ, Braun R, Reimers M, Kumamoto K, Hughes D, Altorki NK, Casson AG, Liu CG, Wang XW, Yanaihara N, Hagiwara N, Dannenberg AJ, Miyashita M, Croce CM, Harris CC: MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival. Clin Cancer Res 2009, 15(19):6192-6200.
• [3]Feber A, Xi L, Pennathur A, Gooding WE, Bandla S, Wu M, Luketich JD, Godfrey TE, Litle VR: MicroRNA prognostic signature for nodal metastases and survival in esophageal adenocarcinoma. Ann Thorac Surg 2011, 91(5):1523-1530.
• [4]Su M, Liu M, Tian DP, Li XY, Zhang GH, Yang HL, Fan X, Huang HH, Gao YX: Temporal trends of esophageal cancer during 1995-2004 in Nanao Island, an extremely high-risk area in China. Eur J Epidemiol 2007, 22(1):43-48.
• [5]Enzinger PC, Mayer RJ: Esophageal cancer. N Engl J Med 2003, 349(23):2241-2252.
• [6]Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB: Prediction of mammalian microRNA targets. Cell 2003, 115(7):787-798.
• [7]Xiong J, Du Q, Liang Z: Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein. Oncogene 2010, 29(35):4980-4988.
• [8]Bar N, Dikstein R: miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. PLoS One 2010, 5(5):e10859.
• [9]Ting Y, Medina DJ, Strair RK, Schaar DG: Differentiation-associated miR-22 represses max expression and inhibits cell cycle progression. Biochem Biophys Res Commun 2010, 394(3):606-611.
• [10]Tsuchiya N, Izumiya M, Ogata-Kawata H, Okamoto K, Fujiwara Y, Nakai M, Okabe A, Schetter AJ, Bowman ED, Midorikawa Y, Sugiyama Y, Aburatani H, Harris CC, Nakagama H: Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21. Cancer Res 2011, 71(13):4628-4639.
• [11]Kong LM, Liao CG, Zhang Y, Xu J, Li Y, Huang W, Zhang Y, Bian H, Chen ZN: A regulatory loop involving miR-22, Sp1, and c-Myc Modulates CD147 expression in breast cancer invasion and metastasis. Cancer Res 2014, 74(14):3764-3778.
• [12]Lin Y, Totsuka Y, He Y, Kikuchi S, Qiao Y, Ueda J, Wei W, Inoue M, Tanaka H: Epidemiology of esophageal cancer in Japan and China. J Epidemiol 2013, 23(4):233-242.
• [13]Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R: Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 2008, 26(7):1086-1092.
• [14]Zhang J, Yang Y, Yang T, Liu Y, Li A, Fu S, Wu M, Pan Z, Zhou W: microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity. Br J Cancer 2010, 103(8):1215-1220.
• [15]Oue N, Aung PP, Mitani Y, Kuniyasu H, Nakayama H, Yasui W: Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression. Oncology 2005, 69(Suppl 1):17-22.
• [16]Gupta GP, Massague J: Cancer metastasis: building a framework. Cell 2006, 127(4):679-695.
• [17]Klein CA: Cancer. The metastasis cascade. Science 2008, 321(5897):1785-1787.
• [18]Sreekumar R, Sayan BS, Mirnezami AH, Sayan AE: MicroRNA control of invasion and metastasis pathways. Front Genet 2011, 2:58.
• [19]Andl CD, Mizushima T, Nakagawa H, Oyama K, Harada H, Chruma K, Herlyn M, Rustgi AK: Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo. J Biol Chem 2003, 278(3):1824-1830.
• [20]Li H, Zheng D, Zhang B, Liu L, Ou J, Chen W, Xiong S, Gu Y, Yang J: Mir-208 promotes cell proliferation by repressing SOX6 expression in human esophageal squamous cell carcinoma. J Transl Med 2014, 12(1):196. BioMed Central Full Text
• [21]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001, 25(4):402-408.
• [22]Liao CG, Kong LM, Song F, Xing JL, Wang LX, Sun ZJ, Tang H, Yao H, Zhang Y, Wang L, Wang Y, Yang XM, Li Y, Chen ZN: Characterization of basigin isoforms and the inhibitory function of basigin-3 in human hepatocellular carcinoma proliferation and invasion. Mol Cell Biol 2011, 31(13):2591-2604.
• [23]Patel JB, Appaiah HN, Burnett RM, Bhat-Nakshatri P, Wang G, Mehta R, Badve S, Thomson MJ, Hammond S, Steeg P, Liu Y, Nakshatri H: Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22. Oncogene 2011, 30(11):1290-1301.