MicroRNAs in lung cancer

Abstract

Lung cancer (LC) is a serious public health problem responsible for the majority of cancer deaths and comorbidities in developed countries. Tobacco smoking is considered the main risk factor for LC; however, only a few smokers will be affected by this cancer. Current screening methods are focused on identifying the early stages of this malignancy. Thus, new data concerning the roles of microRNA alterations in inflammation, epithelial-mesenchymal transition and lung disease have increased hope about LC pathogenesis, diagnosis, treatment and prognosis. MicroRNA mechanisms include angiogenesis promotion, cell cycle regulation by modulating cellular proliferation and apoptosis, and migration and invasion inhibition. In this context, this manuscript reviews the current information about many important microRNAs as they relate to the initiation and progression of LC.

Keywords: epithelial mesenchymal transition; inflammation; interleukin 1; lung cancer; microRNAs.

Figure 1. Chronic inflammation, a key promoting factor of lung tumorigenesis, is associated to secretion of cytokines including tumour necrosis factor α (TNF-α), interleukin 1 (IL-1), IL-6 and IL-8, and molecules such as cyclooxygenase-2 (COX-2) that are defined as “alarm cytokines”

TNF-α is determinant to initiate and regulate the cytokine cascade by triggering the release of IL-1β and IL-6. IL-6 and IL-8 play different roles at a systemic level, being both inducible by IL-1β. IL-6 stimulates secretion of C-reactive protein that is an important inflammatory biomarker. High levels of IL-1β in the tumour microenvironment is directly associated with bad prognosis, mainly because IL-1β promotes tumour invasiveness by angiogenesis induction, activation of myeloid-derived suppressor cells and macrophages type M2.