Epithelial-to-Mesenchymal Transition and MicroRNAs in Lung Cancer

Abstract

Despite major advances, non-small cell lung cancer (NSCLC) remains the major cause of cancer-related death in developed countries. Metastasis and drug resistance are the main factors contributing to relapse and death. Epithelial-to-mesenchymal transition (EMT) is a complex molecular and cellular process involved in tissue remodelling that was extensively studied as an actor of tumour progression, metastasis and drug resistance in many cancer types and in lung cancers. Here we described with an emphasis on NSCLC how the changes in signalling pathways, transcription factors expression or microRNAs that occur in cancer promote EMT. Understanding the biology of EMT will help to define reversing process and treatment strategies. We will see that this complex mechanism is related to inflammation, cell mobility and stem cell features and that it is a dynamic process. The existence of intermediate phenotypes and tumour heterogeneity may be debated in the literature concerning EMT markers, EMT signatures and clinical consequences in NSCLC. However, given the role of EMT in metastasis and in drug resistance the development of EMT inhibitors is an interesting approach to counteract tumour progression and drug resistance. This review describes EMT involvement in cancer with an emphasis on NSCLC and microRNA regulation.

MicroRNA‐331‐3p inhibits epithelial‐mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/β‐catenin axis in non‐small‐cell lung cancer

“…Non‐small‐cell lung cancer has become one of the deadliest malignancies in the world, but the molecular mechanisms involved in NSCLC development are not fully understood. Recent studies revealed that miRNAs play vital roles in the tumorigenesis and progression of NSCLC . In the present study, we focused on the antimetastatic function of miR‐331‐3p in NSCLC.…”

“…Recent studies revealed that miRNAs play vital roles in the tumorigenesis and progression of NSCLC. 28 In the present study, we focused on the antimetastatic function of miR-331-3p in NSCLC. The abnormal expression of miR-331-3p has been found in many types of carcinomas, but the evidence on its biological functions in the tumorigenesis of these cancers is conflicting.…”

CircRNA CDR1as knockdown inhibits progression of non‐small‐cell lung cancer by regulating miR‐219a‐5p/SOX5 axis

“…29 To investigate the potential value of this circRNA in NSCLC, loss-of-function experiments were performed to confirm the anti-proliferation and anti-metastasis roles of circCDR1as silencing in NSCLC, which was similar to the previous report by Zhang et al 16 Moreover, epithelial-to-mesenchymal transition has been regarded as an important mechanism involved in the regulation of development and metastasis of lung cancer. 30,31 Hence, whether circCDR1as can promote cell growth, migration and invasion by inducing epithelial-tomesenchymal transition should be explored in the future.…”

KIF2C exerts an oncogenic role in nonsmall cell lung cancer and is negatively regulated by miR‐325‐3p

“…In addition, more than 40% of patients with early‐stage NSCLC have received treatment will have relapses . It has been currently confirmed that the occurrence of lung cancer had a certain correlation with the abnormal expression of various oncogenes and tumour suppressors, yet the carcinogenic mechanisms of oncogenes and tumour suppressors are complicated . In recent years, a significant progress has been made in the study of lung cancer‐related genes.…”