miR-146b-5p Enhances the Sensitivity of NSCLC to EGFR Tyrosine Kinase Inhibitors by Regulating the IRAK1/NF-κB Pathway

Liu, Yinan; Tsai, Meng‐Feng; Wu, Shang‐Gin; Chang, Tzu‐Hua; Tsai, Tzu‐Hsiu; Gow, Chien‐Hung; Wang, Hsin‐Yi; Shih, Jin‐Yuan

doi:10.1016/j.omtn.2020.09.015

Cited by 34 publications

(33 citation statements)

References 53 publications

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“…Overexpression of miR-146-5p in the resistant cells enhanced their sensitivity to EGFR TK inhibitors. Similar observations were noticed in osimertinib resistant primary cancer cells in both EGFR-dependent and independent manner [ 261 ]. Mechanistically, miR-146b-5p targets interleukin 1 receptor-associated kinase 1 (IRAK1) by downregulating NF-κB and related cytokine production (IL-6 and IL-8).…”

Section: Introductionsupporting

confidence: 84%

“…Mechanistically, miR-146b-5p targets interleukin 1 receptor-associated kinase 1 (IRAK1) by downregulating NF-κB and related cytokine production (IL-6 and IL-8). Thus, miR-146b-5p has the potential to target IRAK1/NF-κB signaling, regulating EGFR TK inhibitor resistance, and may help combat resistance associated with TK inhibitors [ 261 ]. MicroRNA-506 (miR-506) functions as a tumor suppressor in multiple cancers, including LC [ 262 – 264 ].…”

Section: Introductionmentioning

confidence: 99%

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RNA-based therapies: A cog in the wheel of lung cancer defense

et al. 2021

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Lung cancer (LC) is a heterogeneous disease consisting mainly of two subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), and remains the leading cause of death worldwide. Despite recent advances in therapies, the overall 5-year survival rate of LC remains less than 20%. The efficacy of current therapeutic approaches is compromised by inherent or acquired drug-resistance and severe off-target effects. Therefore, the identification and development of innovative and effective therapeutic approaches are critically desired for LC. The development of RNA-mediated gene inhibition technologies was a turning point in the field of RNA biology. The critical regulatory role of different RNAs in multiple cancer pathways makes them a rich source of targets and innovative tools for developing anticancer therapies. The identification of antisense sequences, short interfering RNAs (siRNAs), microRNAs (miRNAs or miRs), anti-miRs, and mRNA-based platforms holds great promise in preclinical and early clinical evaluation against LC. In the last decade, RNA-based therapies have substantially expanded and tested in clinical trials for multiple malignancies, including LC. This article describes the current understanding of various aspects of RNA-based therapeutics, including modern platforms, modifications, and combinations with chemo-/immunotherapies that have translational potential for LC therapies.

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Section: Introductionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

RNA-based therapies: A cog in the wheel of lung cancer defense

et al. 2021

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“…It has been reported that miRNAs play a crucial role in cancer drug resistance ( 106 ). In NSCLC resistant to EGFR TKIs, exogenous miR-146b-5p in EGFR TKI-resistant cells could promote the cell apoptosis induced by EGFR TKIs via regulating the IRAK1/NF-κB pathway ( 107 ). In addition, miR-675-3p, which was from GC-secreted extracellular vesicles (GC-EVs), could enhance cisplatin resistance in vivo via targeting CXXC4 ( 108 ).…”

Section: M6a Modification Contributes To Cancer Drug Resistancementioning

confidence: 99%

m6A Modification in Non-Coding RNA: The Role in Cancer Drug Resistance

Chen

Guo

et al. 2021

Front. Oncol.

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Cancer drug resistance has always been a major difficulty in cancer therapy. In the face of drug pressure, resistant cancer cells show complex molecular mechanisms including epigenetic changes to maintain survival. Studies prove that cancer cells exhibit abnormal m6A modification after acquiring drug resistance. m6A modification in the target RNA including non-coding RNA can be a controller to determine the fate and metabolism of RNA by regulating their stability, subcellular localization, or translation. In particular, m6A-modified non-coding RNA plays multiple roles in multiple drug-resistant cancer cells, which can be a target for cancer drug resistance. Here, we provide an overview of the complex regulatory mechanisms of m6A-modified non-coding RNA in cancer drug resistance, and we discuss its potential value and challenges in clinical applications.

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“…Clinical analysis revealed a significantly higher miR-146b-5p expression in pleural effusions-isolated lung cancer cells from treatment-naive patients than acquiring resistance patients to EGFR-TKI treatment [172,[229][230][231][232]. Further, ectopic expression of miR-146b-5p improved EGFR-TKI-induced apoptosis in EGFR-TKI-resistant cells, EGFR-independent and -dependent osimertinib-resistant primary cancer cells (PE2988 and PE3479).…”

Section: Other Egfr-tkimentioning

confidence: 99%

“…EGFR is frequently activated in a wide range of solid tumors, representing an important therapeutic target [36,167]. Several EGFR-TKIs, including but not limited to erlotinib, gefitinib, afatinib, osimertinib, and icotinib showed efficient therapeutic activities in NSCLC patients harboring EGFR mutations [15, [19][20][21]33,41,52,71,73,76,[168][169][170][171][172][173]. Although primary responses to EGFR-TKIs in NSCLC patients have been shown, their effectiveness is frequently restricted by drug resistance development [10,148,150,174].…”

Section: Effect Of Mirnas On the Chemosensitivity To Egfr-tkismentioning

confidence: 99%

Cell Behavior of Non-Small Cell Lung Cancer Is at EGFR and MicroRNAs Hands

Ibrahim

Abdel-Mawgood

2021

IJMS

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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.

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miR-146b-5p Enhances the Sensitivity of NSCLC to EGFR Tyrosine Kinase Inhibitors by Regulating the IRAK1/NF-κB Pathway

Cited by 34 publications

References 53 publications

RNA-based therapies: A cog in the wheel of lung cancer defense

RNA-based therapies: A cog in the wheel of lung cancer defense

m6A Modification in Non-Coding RNA: The Role in Cancer Drug Resistance

Cell Behavior of Non-Small Cell Lung Cancer Is at EGFR and MicroRNAs Hands

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