Relationship between DLK1 gene promoter region DNA methylation and non-small cell lung cancer biological behavior Retraction in /10.3892/ol.2020.11577

Zhong,Zhaokui; Ye,Yongting; Guo,Wei; He,Yi; Hu,Weicai

doi:10.3892/ol.2017.6019

Relationship between DLK1 gene promoter region DNA methylation and non-small cell lung cancer biological behavior

Retraction in: /10.3892/ol.2020.11577

Authors:
- Zhaokui Zhong
- Yongting Ye
- Wei Guo
- Yi He
- Weicai Hu
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Affiliations: Department of Thoracic Surgery, Central Hospital of Zhumadian, Zhumadian, Henan 463000, P.R. China, Department of Internal Medicine, The Fourth People's Hospital of Zhumadian, Zhumadian, Henan 463000, P.R. China, Department of Thoracic Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China
Published online on: April 10, 2017 https://doi.org/10.3892/ol.2017.6019
Pages: 4123-4126
Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

We investigated the possible association between DLKI gene promoter region methylation and the increased invasion capacity of non-small cell lung cancer (NSCLC). Lung cancer cell line H1299, as well as the gene transfection and RNA interference technology were used to build DLK gene overexpression and knockdown cells. An in vitro invasion assay was performed to observe the changes in the invasion ability of lung cancer cells. Western blot analysis was used to verify Notchl and matrix metalloproteinase-9 (MMP-9) expression levels and a sulfurous acid sequencing technique was used to test the DNA methylation level in the promoter region. Our results showed that the invasion ability of cells in the overexpression group was significantly enhanced. This ability was considerably reduced in the knockdown group. The Notchl and MMP-9 expression level increased significantly in the overexpression group, while it was reduced considerably in the knockdown group. We detected significantly lower levels of DNA methylation in the promoter region in the overexpression group. It was concluded that methylation of the DLK1 gene promoter region increased the invasion ability of NSCLC. Furthermore, it is possible that this process is related to the Notch signaling pathway.

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1	Yung KW, Yung TT, Chung CY, Tong GT, Liu Y, Henderson J, Welbeck D and Oseni S: Principles of cancer staging. Asian Pac J Surg Oncol. 1:1–16. 2015.
2	Guo F, Guo L, Li Y, Zhou Q and Li Z: MALAT1 is an oncogenic long non-coding RNA associated with tumor invasion in non-small cell lung cancer regulated by DNA methylation. Int J Clin Exp Pathol. 8:15903–15910. 2015.PubMed/NCBI
3	Liu Y, Tan J, Li L, Li S, Zou S, Zhang Y, Zhang X, Ling B, Han N, Guo S, et al: Study on the molecular mechanisms of dlk1 stimulated lung cancer cell proliferation. Zhongguo Fei Ai Za Zhi. 13:923–927. 2010.(In Chinese). PubMed/NCBI
4	Yue LZ, Fu R, Wang HQ, Li LJ, Ruan EB, Wang GJ, Qu W, Liang Y, Guan J, Wu YH, et al: Expression of DLK1 gene in the bone marrow cells of patients with myelodysplastic syndromes and its clinical significance. Cancer Biol Med. 9:188–191. 2012.PubMed/NCBI
5	Sakajiri S, O'kelly J, Yin D, Miller CW, Hofmann WK, Oshimi K, Shih LY, Kim KH, Sul HS, Jensen CH, et al: Dlk1 in normal and abnormal hematopoiesis. Leukemia. 19:1404–1410. 2005. View Article : Google Scholar : PubMed/NCBI
6	Nueda ML, Baladrón V, Sánchez-Solana B, Ballesteros MA and Laborda J: The EGF-like protein dlk1 inhibits notch signaling and potentiates adipogenesis of mesenchymal cells. J Mol Biol. 367:1281–1293. 2007. View Article : Google Scholar : PubMed/NCBI
7	Li L, Tan J, Zhang Y, Han N, Di X, Xiao T, Cheng S, Gao Y and Liu Y: DLK1 promotes lung cancer cell invasion through upregulation of MMP9 expression depending on Notch signaling. PLoS One. 9:e915092014. View Article : Google Scholar : PubMed/NCBI
8	Tabouret E, Bertucci F, Pierga JY, Petit T, Levy C, Ferrero JM, Campone M, Gligorov J, Lerebours F, Roché H, et al: MMP2 and MMP9 serum levels are associated with favorable outcome in patients with inflammatory breast cancer treated with bevacizumab-based neoadjuvant chemotherapy in the BEVERLY-2 study. Oncotarget. 23:15–16. 2016.
9	Moz S, Basso D, Padoan A, Bozzato D, Fogar P, Zambon CF, Pelloso M, Sperti C, de Kreutzenberg S Vigili, Pasquali C, et al: Blood expression of matrix metalloproteinases 8 and 9 and of their inducers S100A8 and S100A9 supports diagnosis and prognosis of PDAC-associated diabetes mellitus. Clin Chim Acta. 456:24–30. 2016. View Article : Google Scholar : PubMed/NCBI
10	Pogribny IP and Beland FA: DNA hypomethylation in the origin and pathogenesis of human diseases. Cell Mol Life Sci. 66:2249–2261. 2009. View Article : Google Scholar : PubMed/NCBI
11	Esteller M: Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 8:286–298. 2007. View Article : Google Scholar : PubMed/NCBI
12	Esteller M and Herman JG: Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol. 196:1–7. 2002. View Article : Google Scholar : PubMed/NCBI
13	Suter CM, Martin DI and Ward RL: Germline epimutation of MLH1 in individuals with multiple cancers. Nat Genet. 36:497–501. 2004. View Article : Google Scholar : PubMed/NCBI
14	Cui H, Onyango P, Brandenburg S, Wu Y, Hsieh CL and Feinberg AP: Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res. 62:6442–6446. 2002.PubMed/NCBI
15	Kanai Y: Genome-wide DNA methylation profiles in precancerous conditions and cancers. Cancer Sci. 101:36–45. 2010. View Article : Google Scholar : PubMed/NCBI
16	Belinsky SA: Gene-promoter hypermethylation as a biomarker in lung cancer. Nat Rev Cancer. 4:707–717. 2004. View Article : Google Scholar : PubMed/NCBI
17	de Caceres I Ibanez, Cortes-Sempere M, Moratilla C, Machado-Pinilla R, Rodriguez-Fanjul V, Manguán-García C, Cejas P, López-Ríos F, Paz-Ares L, de CastroCarpeño J, et al: IGFBP-3 hypermethylation-derived deficiency mediates cisplatin resistance in non-small-cell lung cancer. Oncogene. 29:1681–1690. 2010. View Article : Google Scholar : PubMed/NCBI
18	Yang X, Lay F, Han H and Jones PA: Targeting DNA methylation for epigenetic therapy. Trends Pharmacol Sci. 31:536–546. 2010. View Article : Google Scholar : PubMed/NCBI
19	Herman JG, Graff JR, Myöhänen S, Nelkin BD and Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 93:pp. 9821–9826. 1996; View Article : Google Scholar : PubMed/NCBI
20	Wani K and Aldape KD: PCR techniques in characterizing DNA methylation. Methods Mol Biol. 1392:177–186. 2016. View Article : Google Scholar : PubMed/NCBI