Abstract
Lung cancer is a complex disease associated with gene mutations, particularly mutations of Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) and epidermal growth factor receptor (EGFR). Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are the two major types of lung cancer. The former includes most lung cancers (85%) and are commonly associated with EGFR mutations. Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, and osimertinib, are effective therapeutic agents in EGFR-mutated NSCLC. However, their effectiveness is limited by the development (acquired) or presence of intrinsic drug resistance. MicroRNAs (miRNAs) are key gene regulators that play a profound role in the development and outcomes for NSCLC via their role as oncogenes or oncosuppressors. The regulatory role of miRNA-dependent EGFR crosstalk depends on EGFR signaling pathway, including Rat Sarcoma/Rapidly Accelerated Fibrosarcoma/Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase 1/2 (Ras/Raf/MEK/ERK1/2), Signal Transducer and Activator of Transcription (STAT), Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-kB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Janus kinase 1 (JAK1), and growth factor receptor-bound protein 2 (GRB2). Dysregulated expression of miRNAs affects sensitivity to treatment with EGFR-TKIs. Thus, abnormalities in miRNA-dependent EGFR crosstalk can be used as diagnostic and prognostic markers, as well as therapeutic targets in NSCLC. In this review, we present an overview of miRNA-dependent EGFR expression regulation, which modulates the behavior and progression of NSCLC.
Highlights
Lung cancer is the foremost cancer type in terms of incidence and mortality rates in men and women [1,2,3]
The miRNA–epidermal growth factor receptor (EGFR) regulatory network can control many cellular processes. miRNA-dependent EGFR expression and/or hyperactivation have been associated with lung cancer cell behavior, including cell survival, resisting cell apoptosis, cell migration and invasion, proliferative activity, and modulating cell sensitivity to tyrosine kinase inhibitors (TKIs)
The use of EGFR-TKIs has considerably improved the prognosis of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations
Summary
Lung cancer is the foremost cancer type in terms of incidence and mortality rates in men and women [1,2,3]. The transduction of bronchial epithelial BEAS-2B cells with retroviral vectors expressing KRASG12V (Kirsten Rat Sarcoma Viral Oncogene Homolog) and monitoring miRNA expression patterns by microarray analysis was performed to identify miRNAs implicated in EGFR signaling in NSCLC patients. This approach could define miR-29b as an important target for upregulation by mutant KRAS, wherein the. MiR-29b expression can cause cells to shift from extrinsic to intrinsic apoptosis mechanisms From these data, miR-29b can act as an oncogene or a tumor suppressor gene, depending on the signaling context [41,43,44,45,46]. EGFR Overexpression/Hyperactivation and miRNA Expression Pattern: Effects on NSCLC Cell Behavior
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