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Article

Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer

  • Authors:
    • Yong Chen
    • Lingfeng Min
    • Xizhi Zhang
    • Suwei Hu
    • Buhai Wang
    • Wei  Liu
    • Rui Wang
    • Xuewen Gu
    • Weigan Shen
    • Houning Lv
    • Jing Zou
    • Yuexiang Chen
    • Xingxiang Xu
    • Longbang Chen
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Respiratory Medicine, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Gynecology and Obstetrics, Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Medical Oncology, Hebei Medical University Fourth Hospital, Shijiazhuang, Hebei 050011, P.R. China, Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China, Department of Pathology, Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Cytobiology, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
  • Pages: 1832-1840
    |
    Published online on: July 9, 2013
       https://doi.org/10.3892/or.2013.2611
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Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and only 15% of lung cancer patients live more than 5 years. microRNAs (miRNAs) are endogenously expressed non-coding RNAs, and dysregulation of miRNAs is a common feature in human cancers including lung cancer. In this study, we describe the epigenetic regulation of miRNA-148a and its prognostic value in NSCLC. Due to hypermethylation of the miRNA‑148a encoding region, the expression levels of miRNA-148a were decreased in NSCLC tissues and cells. Decreased miRNA‑148a expression was associated with lymph node metastasis, advanced clinical stage and shortened disease-free survival and overall survival in NSCLC, and was an independent prognostic factor for overall survival in multivariate analysis. In vitro, overexpression of miRNA-148a significantly suppressed the migratory and invasive abilities of A549 and H1299 lung cancer cells. Enforced expression of miRNA-148a in lung cancer cell lines resulted in a significant reduction in the expression of DNMT1. This, in turn, led to a decrease in DNA methylation of the tumor-suppressor gene E-cadherin and induced an increase in the protein levels of E-cadherin. By understanding the function and molecular mechanism of miRNA-148a in NSCLC, miRNA-148a may have therapeutic potential to suppress lung cancer metastasis.
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1 

Jemal A, Tiwari RC, Murray T, et al: Cancer statistics, 2004. CA Cancer J Clin. 54:8–29. 2004. View Article : Google Scholar

2 

Minna JD, Roth JA and Gazdar AF: Focus on lung cancer. Cancer Cell. 1:49–52. 2002. View Article : Google Scholar

3 

Dykxhoorn DM: MicroRNAs and metastasis: little RNAs go a long way. Cancer Res. 70:6401–6406. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Yanaihara N, Caplen N, Bowman E, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9:189–198. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Farazi TA, Spitzer JI, Morozov P and Tuschl T: miRNAs in human cancer. J Pathol. 223:102–115. 2011. View Article : Google Scholar

6 

Garzon R, Fabbri M, Cimmino A, Calin GA and Croce CM: MicroRNA expression and function in cancer. Trends Mol Med. 12:580–587. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Zhang B, Pan X, Cobb GP and Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Schetter AJ, Leung SY, Sohn JJ, et al: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 299:425–436. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Hummel R, Hussey DJ, Michael MZ, et al: MiRNAs and their association with locoregional staging and survival following surgery for esophageal carcinoma. Ann Surg Oncol. 18:253–260. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Langevin SM, Stone RA, Bunker CH, et al: MicroRNA-137 promoter methylation is associated with poorer overall survival in patients with squamous cell carcinoma of the head and neck. Cancer. 117:1454–1462. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Watanabe K, Emoto N, Hamano E, et al: Genome structure-based screening identified epigenetically silenced microRNA associated with invasiveness in non-small-cell lung cancer. Int J Cancer. 130:2580–2590. 2012. View Article : Google Scholar

12 

Visone R, Rassenti LZ, Veronese A, et al: Karyotype-specific microRNA signature in chronic lymphocytic leukemia. Blood. 114:3872–3879. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Magrelli A, Azzalin G, Salvatore M, et al: Altered microRNA expression patterns in hepatoblastoma patients. Transl Oncol. 2:157–163. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Xu Q, Jiang Y, Yin Y, et al: A regulatory circuit of miR-148a/152 and DNMT1 in modulating cell transformation and tumor angiogenesis through IGF-IR and IRS1. J Mol Cell Biol. 5:3–13. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Ueda T, Volinia S, Okumura H, et al: Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 11:136–146. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Katada T, Ishiguro H, Kuwabara Y, et al: microRNA expression profile in undifferentiated gastric cancer. Int J Oncol. 34:537–542. 2009.PubMed/NCBI

17 

Chen Y, Song Y, Wang Z, et al: Altered expression of MiR-148a and MiR-152 in gastrointestinal cancers and its clinical significance. J Gastrointest Surg. 14:1170–1179. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Zhang H, Li Y, Huang Q, et al: MiR-148a promotes apoptosis by targeting Bcl-2 in colorectal cancer. Cell Death Differ. 18:1702–1710. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Zhu A, Xia J, Zuo J, et al: MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in gastric cancer. Med Oncol. 29:2701–2709. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Liffers ST, Munding JB, Vogt M, et al: MicroRNA-148a is down-regulated in human pancreatic ductal adenocarcinomas and regulates cell survival by targeting CDC25B. Lab Invest. 91:1472–1479. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Lujambio A, Calin GA, Villanueva A, et al: A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA. 105:13556–13561. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Zheng B, Liang L, Wang C, et al: MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res. 17:7574–7583. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Reddel RR, Ke Y, Gerwin BI, et al: Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprecipitation with a plasmid containing SV40 early region genes. Cancer Res. 48:1904–1909. 1988.

24 

Hanoun N, Delpu Y, Suriawinata AA, et al: The silencing of microRNA 148a production by DNA hypermethylation is an early event in pancreatic carcinogenesis. Clin Chem. 56:1107–1118. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Wang G, Hu X, Lu C, Su C, Luo S and Luo ZW: Promoter-hypermethylation associated defective expression of E-cadherin in primary non-small cell lung cancer. Lung Cancer. 62:162–172. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Pan W, Zhu S, Yuan M, et al: MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol. 184:6773–6781. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Xi Y, Nakajima G, Gavin E, et al: Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA. 13:1668–1674. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Zhang X, Chen J, Radcliffe T, Lebrun DP, Tron VA and Feilotter H: An array-based analysis of microRNA expression comparing matched frozen and formalin-fixed paraffin-embedded human tissue samples. J Mol Diagn. 10:513–519. 2008. View Article : Google Scholar

29 

Leite KR, Canavez JM, Reis ST, et al: miRNA analysis of prostate cancer by quantitative real time PCR: comparison between formalin-fixed paraffin embedded and fresh-frozen tissue. Urol Oncol. 29:533–537. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar

31 

Calin GA and Croce CM: MicroRNA-cancer connection: the beginning of a new tale. Cancer Res. 66:7390–7394. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Qiu X, Qiao F, Su X, Zhao Z and Fan H: Epigenetic activation of E-cadherin is a candidate therapeutic target in human hepatocellular carcinoma. Exp Ther Med. 1:519–523. 2010.PubMed/NCBI

33 

Huang J, Wang Y, Guo Y and Sun S: Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology. 52:60–70. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Shimamoto T, Ohyashiki JH, Hirano T, Kato H and Ohyashiki K: Hypermethylation of E-cadherin gene is frequent and independent of p16INK4A methylation in non-small cell lung cancer: Potential prognostic implication. Oncol Rep. 12:389–395. 2004.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chen Y, Min L, Zhang X, Hu S, Wang B, Liu W, Wang R, Gu X, Shen W, Lv H, Lv H, et al: Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer. Oncol Rep 30: 1832-1840, 2013.
APA
Chen, Y., Min, L., Zhang, X., Hu, S., Wang, B., Liu, W. ... Chen, L. (2013). Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer. Oncology Reports, 30, 1832-1840. https://doi.org/10.3892/or.2013.2611
MLA
Chen, Y., Min, L., Zhang, X., Hu, S., Wang, B., Liu, W., Wang, R., Gu, X., Shen, W., Lv, H., Zou, J., Chen, Y., Xu, X., Chen, L."Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer". Oncology Reports 30.4 (2013): 1832-1840.
Chicago
Chen, Y., Min, L., Zhang, X., Hu, S., Wang, B., Liu, W., Wang, R., Gu, X., Shen, W., Lv, H., Zou, J., Chen, Y., Xu, X., Chen, L."Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer". Oncology Reports 30, no. 4 (2013): 1832-1840. https://doi.org/10.3892/or.2013.2611
Copy and paste a formatted citation
x
Spandidos Publications style
Chen Y, Min L, Zhang X, Hu S, Wang B, Liu W, Wang R, Gu X, Shen W, Lv H, Lv H, et al: Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer. Oncol Rep 30: 1832-1840, 2013.
APA
Chen, Y., Min, L., Zhang, X., Hu, S., Wang, B., Liu, W. ... Chen, L. (2013). Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer. Oncology Reports, 30, 1832-1840. https://doi.org/10.3892/or.2013.2611
MLA
Chen, Y., Min, L., Zhang, X., Hu, S., Wang, B., Liu, W., Wang, R., Gu, X., Shen, W., Lv, H., Zou, J., Chen, Y., Xu, X., Chen, L."Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer". Oncology Reports 30.4 (2013): 1832-1840.
Chicago
Chen, Y., Min, L., Zhang, X., Hu, S., Wang, B., Liu, W., Wang, R., Gu, X., Shen, W., Lv, H., Zou, J., Chen, Y., Xu, X., Chen, L."Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer". Oncology Reports 30, no. 4 (2013): 1832-1840. https://doi.org/10.3892/or.2013.2611
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