Interleukin-1β-mediated suppression of microRNA-101 and upregulation of enhancer of zeste homolog 2 is involved in particle-induced lung cancer

Lung cancer may be a result of complex factors. Small mineral particle is the well-known inducer of lung cancer. Previous study revealed the high morbidity of lung cancer in Xuan Wei in China, and the main cause of lung cancer is the use of smoky coal there. And it is generally accepted that chronic inflammation induced by small mineral particle may be a cause of lung cancer. But the relationship between chronic lung inflammation and lung cancer is largely unknown. In the present study, we found that silica particle was able to induce the secretion of interleukin-1β from a Xuan Wei lung cancer cell line, XWLC-05. At the same time, microRNA-101 (mir-101) was found to be downregulated by the treatment of silica particle. Interestingly, the interleukin 1 receptor antagonist and interleukin-1β antibody can reduce silica particle-induced downregulation of mir-101. Twenty-four Xuan Wei lung tumor tissues were collected to detect the expression level of mir-101 and enhancer of zeste homolog 2 (EZH2), which is the potential target of mir-101. The results showed that mir-101 was down-regulated and EZH2 were upregulated. Subsequently, the roles of mir-101 and EZH2 in tumor growth and progression in vitro were tested. Overexpression of mir-101 mimics was able to suppress the expression of EZH2 in XWLC-05 cells. And this resulted in the inhibited tumor cell growth and attenuated cell migration. The results in the present study showed that particle can induce the secretion of interleukin-1β. Interleukin-1β subsequently induces the downregulation of mir-101, which may result in the upregulated level of EZH2, and occurrence of lung cancer. We for the first time proposed the role interleukin-1β–mir-101–EZH2 axes in the particle-induced lung cancer. Further study may be needed to decipher the detailed mechanism involved.