Field Cancerization in NSCLC: A New Perspective on MicroRNAs in Macrophage Polarization

Abstract

Lung cancer is currently the first cause of cancer-related death. The major lung cancer subtype is non-small cell lung cancers (NSCLC), which accounts for approximatively 85% of cases. The major carcinogenic associated with lung cancer is tobacco smoke, which produces long-lasting and progressive damage to the respiratory tract. The progressive and diffuse alterations that occur in the respiratory tract of patients with cancer and premalignant lesions have been described as field cancerization. At the level of tumor cells, adjacent tumor microenvironment (TME) and cancerized field are taking place dynamic interactions through direct cell-to-cell communication or through extracellular vesicles. These molecular messages exchanged between tumor and nontumor cells are represented by proteins, noncoding RNAs (ncRNAs) and microRNAs (miRNAs). In this paper, we analyze the miRNA roles in the macrophage polarization at the level of TME and cancerized field in NSCLC. Identifying molecular players that can influence the phenotypic states at the level of malignant cells, tumor microenvironment and cancerized field can provide us new insights into tumor regulatory mechanisms that can be further modulated to restore the immunogenic capacity of the TME. This approach could revert alterations in the cancerized field and could enhance currently available therapy approaches.

Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

“…In this context, we observed an elevated level of miR-146a in pulmonary sarcoidosis inflammation ( 69 ). Concerning miRNAs involvement in TAM polarization miR-146a-5p, miR-324-5p, miR-223-3p, miR-223-5p, miR-21, miR-125a, miR-130a, and miR-155a were characterized as oncogenic miRNA, while, miR-1207 and miR-320a as a tumour suppressor miRNA in lung cancer including non-small-cell lung carcinoma (NSCLC) ( 70 ). These reports thus emphasize the important role of miRNAs in regulating M1/M2 macrophage polarization in lung diseases in general.…”

Regulatory Mechanism of lncRNAs in M1/M2 Macrophages Polarization in the Diseases of Different Etiology

“…Through the study of these lncRNAs in vivo and in vitro , TAMs can be polarized into pro-inflammatory or anti-inflammatory state, so as to develop new strategies to change the phenotype of Mφs . These cell therapies can be further combined with currently available chemotherapy and radiotherapy options to improve therapeutic effectiveness ( 113 ).…”

The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC

“…Wu et al performed a series of comprehensive investigations focused directly on a cohort of NAFLD-related HCC cases and in vivo and in vitro lab-grown study models. M2 to M1 phenotype is an essential transition in cancer development that can reverse the tumor-promoting effects of M2 macrophages [ 227 , 233 , 234 ]. The expression of lncRNA FTX and M1/M2 KCs ratio decreased during the NAFLD conversion to HCC.…”