Epigenetic silencing of CXCL14 induced colorectal cancer migration and invasion

Baoping Cao, Yunsheng Yang, Yuanming Pan, Yan Jia, Malcolm V. Brock, James G. Herman, Mingzhou Guo

Research output: Contribution to journalArticle

Abstract

To explore epigenetic regulation and the impact of chemokine CXCL14 on colorectal cancer, 7 colorectal cancer cell lines, 107 cases of primary colorectal cancer, and 10 cases of normal colorectal mucosa were evaluated in this study. Methylation specific PCR (MSP), semi-quantitative reverse-transcription PCR (RT-PCR), cell proliferation assay, colony formation, and transwell assay were performed for the evaluation. Complete methylation and loss of CXCL14 expression were found in 5 colorectal cancer cell lines. Partial methylation and weak expression were found in two cell lines. CXCL14 was methylated in 79.4% (85/107) of primary human colorectal cancer. No methylation was found in 10 cases of normal colorectal mucosa. Restoration of CXCL14 expression was induced by the 5-aza-2́-deoxycytidine (DAC) treatment. The cell viability was reduced and colony formation was inhibited by restoration of CXCL14 expression in HCT116 cells, a colorectal cancer cell line. The number of invasive and migration cells was reduced by CXCL14. The expression of MMP-2, Vimentin, and NF-κB was suppressed, and the expression of E-cadherin and IκB-α was induced by CXCL14. In conclusion, CXCL14 is frequently methylated in human colorectal cancer and promoter region hypermethylation silenced CXCL14 expression in colorectal cancer cells. Restoration of CXCL14 expression suppressed colorectal cancer proliferation. CXCL14 inhibits colorectal cancer migration, invasion, and epithelial-to-mesenchymal transition (EMT) by suppressing NF-κB signaling.

Original languageEnglish (US)
Pages (from-to)137-147
Number of pages11
JournalDiscovery Medicine
Volume16
Issue number88
StatePublished - Oct 2013

ASJC Scopus subject areas

  • Medicine(all)

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    Cao, B., Yang, Y., Pan, Y., Jia, Y., Brock, M. V., Herman, J. G., & Guo, M. (2013). Epigenetic silencing of CXCL14 induced colorectal cancer migration and invasion. Discovery Medicine, 16(88), 137-147.