MicroRNAs as regulators of cisplatin-resistance in non-small cell lung carcinomas

Abstract

With more than 80% of all diagnosed lung cancer cases, non-small cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. Exact diagnosis is mostly very late and advanced-stage NSCLCs are inoperable at admission. Tailored therapies with tyrosine kinase inhibitors are only available for a minority of patients. Thus, chemotherapy is often the treatment of choice. As first-line chemotherapy for NSCLCs, platinum-based substances (e.g. cisplatin, CDDP) are mainly used. Unfortunately, the positive effects of CDDP are frequently diminished due to development of drug resistance and negative influence of microenvironmental factors like hypoxia. MicroRNAs (miRNAs) are small, non-coding molecules involved in the regulation of gene expression and modification of biological processes like cell proliferation, apoptosis and cell response to chemotherapeutics. Expression of miRNAs is often deregulated in lung cancer compared to corresponding non-malignant tissue. In this review we summarize the present knowledge about the effects of miRNAs on CDDP-resistance in NSCLCs. Further, we focus on miRNAs deregulated by hypoxia, which is an important factor in the development of CDDP-resistance in NSCLCs. This review will contribute to the general understanding of miRNA-regulated biological processes in NSCLC, with special focus on the role of miRNA in CDDP-resistance.