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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 miR-218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of miR-218 in XWLC-05 cells were markedly lower compared with those in immortalized lung epithelial BEAS-2B cells. The present study also demonstrated that overexpression of miR-218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWLC-05 and NSCLC cell line NCI-H157. Additionally, the results revealed that overexpression of miR-218 could induce XWLC-05 and NCI-H157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of miR-218 could lead to a significant increase in phosphatase and tensin homolog (PTEN) and YY1 transcription factor (YY1), and a decrease in B-cell lymphoma 2 (BCL-2) and BMI1 proto-oncogene, polycomb ring finger (BMI-1) at the mRNA and protein level in XWLC-05 and NCI-H157 cell lines. However, we did not observe any remarkable difference in the roles of miR-218 and miR-218-mediated regulation of BCL-2, BMI-1, PTEN and YY1 expression in the progression of Xuanwei lung cancer. In conclusion, miR-218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasing PTEN and YY1 expression, while decreasing BCL-2 and BMI-1 in Xuanwei lung cancer. The results demonstrated that miR-218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of miR-218 may be a novel approach for the treatment of Xuanwei lung cancer. [ABSTRACT FROM AUTHOR]