Methylation Status of the SOCS3 Gene Promoter in H2228 Cells and EML4–ALK-positive Lung Cancer Tissues

• Main Authors: Chunlai LIU, Yongwen LI, Yunlong DONG, Hongbing ZHANG, Ying LI, Hongyu LIU, Jun CHEN
• Format: Article
• Language: zho
• Published: Chinese Anti-Cancer Association; Chinese Antituberculosis Association 2016-09-01
• Series: Chinese Journal of Lung Cancer
• Subjects: Lung neoplasms; Echinoderm microtubule-associated-protein-like 4 (EML4); Anaplastic lymphoma kinase (ALK); Suppressor of cytokine signaling 3 (SOCS3); DNA methylation
• Online Access: http://dx.doi.org/10.3779/j.issn.1009-3419.2016.09.01
• ISSN: 1009-3419; 1999-6187

Background and objective The EML4-ALK fusion gene is a newly discovered driver gene of non-small cell lung cancer and exhibits special clinical and pathological features. The JAK-STAT signaling pathway, an important downstream signaling pathway of EML4-ALK, is aberrantly sustained and activated in EML4-ALK-positive lung cancer cells fusion gene, but the underlying reason remains unknown. The suppressor of cytokine signaling (SOCS) is a negative regulatory factor that mainly inhibits the proliferation, differentiation, and induction of apoptotic cells by inhibiting the JAK-STAT signaling pathway. The aberrant methylation of the SOCS gene leads to inactivation of tumors and abnormal activation of the JAK2-STAT signaling pathway. The aim of this study is to investigate the methylation status of the SOCS3 promoter in EML4-ALK-positive H2228 cells and lung cancer tissues. Methods The methylation status of the SOCS3 promoter in EML4-ALK-positive H2228 lung cancer cells and lung cancer tissues was detected by methylation-specific PCR (MSP) analysis and verified by DNA sequencing. The expression levels of SOCS3 in H2228 cells were detected by Western blot and Real-time PCR analyses after treatment with the DNA methyltransferase inhibitor 5'-Aza-dC. Results MSP and DNA sequencing assay results indicated the presence of SOCS3 promoter methylation in H2228 cells as well as in three cases of seven EML4-ALK-positive lung cancer tissues. The expression level of SOCS3 significantly increased in H2228 cells after 5′-Aza-dC treatment. Conclusion The aerrant methylation of the SOCS3 promoter region in EML4-ALK (+) H2228 cells and lung cancer tissues may be significantly involved in the pathogenesis of EML4-ALK-positive lung cancer.