RESUMO
Lung cancer is the most prevalent and observed type of cancer in Xuanwei County, Yunnan, South China. Lung cancer in this area is called Xuanwei lung cancer. However, its pathogenesis remains largely unknown. To date, a number of studies have shown that microRNA (miR)218 functions as a tumor suppressor in multiple types of cancer. However, the role of miR218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of miR218 in XWLC05 cells were markedly lower compared with those in immortalized lung epithelial BEAS2B cells. The present study also demonstrated that overexpression of miR218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWLC05 and NSCLC cell line NCIH157. Additionally, the results revealed that overexpression of miR218 could induce XWLC05 and NCIH157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of miR218 could lead to a significant increase in phosphatase and tensin homolog (PTEN) and YY1 transcription factor (YY1), and a decrease in Bcell lymphoma 2 (BCL2) and BMI1 protooncogene, polycomb ring finger (BMI1) at the mRNA and protein level in XWLC05 and NCIH157 cell lines. However, we did not observe any remarkable difference in the roles of miR218 and miR218mediated regulation of BCL2, BMI1, PTEN and YY1 expression in the progression of Xuanwei lung cancer. In conclusion, miR218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasing PTEN and YY1 expression, while decreasing BCL2 and BMI1 in Xuanwei lung cancer. The results demonstrated that miR218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of miR218 may be a novel approach for the treatment of Xuanwei lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação para Baixo , Neoplasias Pulmonares/genética , MicroRNAs/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , China , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismoRESUMO
OBJECTIVE: To explore the differential gene expressions of chronic hepatitis B (CHB) of Gan depression Pi deficiency syndrome (GDPDS) and Pi-Wei damp-heat syndrome (PWDHS). METHODS: The ulnar venous blood was withdrawn from healthy subjects (26 cases), patients of GDPDS (35 cases) and PWDHS (34 cases) on an empty stomach. The total RNA was extracted using Trizol method. The differential genes were detected using Aglient expression profile chip and screened using randomized variance model. The results were analyzed using GO, Pathway, GeneBank, NCBI, and Geneontology. RESULTS: There were 125 differential genes between CHB patients of GDPDS and those of PWDHS (including 66 up-regulated genes and 59 down-regulated genes), mainly involving in functions of transmembrane transport, response to selenium ion, and regulation of calcium ion-dependent exocytosis. The signal pathway participated in mainly includes cell adhesion molecules, calcium ion signaling pathway, leukocyte trans-endothelial migration. We present gene co-expression networks to find 9 interactions among genes (LOC340508, HIST2H2BE, MPL, FLJ22536, TUBA8, NT5M, EGFL7, PTPRF, TSPAN33), which were mainly involved in immune response, cell growth, DNA damage, signal transduction, inflammatory reaction, and so on. CONCLUSIONS: The differential expression genes existed between CHB patients of GDPDS and those of PWDHS, indicating that Chinese medicine syndrome classification has its own basis for gene expression profile. The genomics research method is expected to provide an objective basis for Chinese medicine syndrome typing.