MiR-21 overexpression is associated with acquired resistance of EGFR-TKI in non-small cell lung cancer

Li, Bing; Ren, Shengxiang; Li, Xuefei; Wang, Yongsheng; Garfield, David H.; Zhou, Shunhua; Chen, Xiaoxia; Su, Chunxia; Chen, Mo; Kuang, Peng; Gao, Guanghui; He, Yayi; Fan, Lihong; Fei, Ke; Zhou, Caicun; Schmit-Bindert, Gerald

doi:10.1016/j.lungcan.2013.11.003

Cited by 157 publications

(142 citation statements)

References 46 publications

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“…Interestingly, another study showed that miR-21 is involved in acquired resistance of EGFR-TKI in NSCLC [150]. The serum miR-21 expression in 25 advanced NSCLC patients treated with EGFR-TKI was significantly higher at the time of acquiring resistance than at baseline (P < 0.01).…”

Section: Mirnas As Biomarkers For Targeted Therapies In Nsclcmentioning

confidence: 99%

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

Florczuk¹,

Szpechcinski²,

Chorostowska‐Wynimko³

2017

Targ Oncol

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Lung cancer is the most common cancer worldwide. Up to 85% of lung cancer cases are diagnosed as nonsmall cell lung cancer (NSCLC). The effectiveness of NSCLC treatment is expected to be improved through the implementation of robust and specific biomarkers. MicroRNAs (miRNAs) are small, non-coding molecules that play a key role in the regulation of basic cellular processes, including differentiation, proliferation and apoptosis, by controlling gene expression at the post-transcriptional level.

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Section: Mirnas As Biomarkers For Targeted Therapies In Nsclcmentioning

confidence: 99%

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

Florczuk¹,

Szpechcinski²,

Chorostowska‐Wynimko³

2017

Targ Oncol

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“…In addition to the well-known platinum-based chemotherapy for lung cancer, miR-21 has been shown to be involved in the resistance to the EGFR inhibitor. EGFR-tyrosine kinase inhibitor (TKI) has been regarded as an important treatment option for NSCLC and miR-21 overexpression was found to be associated with acquired resistance to EGFR-TKI (77,78). A pilot study using plasma miRNA profiles identified miR-21 to be involved in the primary resistance to EGFR-TKI in patients with advanced NSCLC with an activating EGFR mutation.…”

Section: Mir-21 and Solid Tumorsmentioning

confidence: 99%

“…The application of this non-invasive approach may be considered for monitoring responses of lung cancer patients to EGFR-TKI treatment (79). Furthermore, the implication of miR-21 in chemotherapy resistance has been investigated for a wide range of solid cancer types, including pancreatic and prostate cancer, hepatoma, ovarian cancer, glioma, and head and neck, stomach and bladder cancer (Table I) (68)(69)(70)(71)75,(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94). These results support the clinical application of miR-21 inhibition in cancer treatments in the future.…”

Section: Mir-21 and Solid Tumorsmentioning

confidence: 99%

Emerging role of microRNA-21 in cancer

2016

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Abstract. MicroRNAs (miRs) are a class of single-stranded RNA molecules of 15-27 nucleotides in length that regulate gene expression at the post-translational level. miR-21 is one of the earliest identified cancer-promoting 'oncomiRs', targeting numerous tumor suppressor genes associated with proliferation, apoptosis and invasion. The regulation of miR-21 and its role in carcinogenesis have been extensively investigated. Recent studies have focused on the diagnostic and prognostic value of miR-21 as well as its implication in the drug resistance of human malignancies. The further use of miR-21 as a biomarker and target for cancer treatments is likely to improve the outcome for patients with cancer. The present review highlights recent findings associated with the importance of miR-21 in hematological and non-hematological malignancies. IntroductionMicroRNAs (miRs) are a class of naturally occurring short non-coding RNA molecules of 15-27 nucleotides in length that regulate eukaryotic gene expression at the post-transcriptional level. Almost 2,000 human miRNAs have been identified through cloning and/or sequence analysis (1). They have key regulatory roles in the development, differentiation and apoptosis of normal cells, as well as in the determination of the final phenotype of cancer cells, affecting carcinogenesis and metastatic potential (2). miR-21 is an abundantly expressed miRNA in mammalian cells, whose upregulation is associated with numerous types of cancer (3,4). By generation of a conditional miR-21 knock-in mouse, it was demonstrated that miR-21 functions as an oncogene with its overexpression resulting in malignant B-cell lymphoma (5). Indeed, miR-21 was found to be the only consistently upregulated miRNA in a study that profiled 540 clinical samples from cancer patients (6). The majority of studies on miR-21 have focused on its role in carcinogenesis and its clinical application. miR-21 is also expressed in hematopoietic cells of the immune system, including B/T cells, monocytes, macrophages and dendritic cells. High miR-21 levels are, therefore, considered to be a marker of immune cell activation (7). Regarding pathological necrosis, miR-21 enhances cellular necrosis by negatively regulating tumor suppressor genes associated with the death receptor-mediated intrinsic apoptotic pathway (8). Biological function of miR-21The biological functions of various miRNAs, including miR-21, have been extensively investigated and miR-21 is

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“…miR-21 is overexpressed in several human malignancies and has been implicated in various biological processes, including cell proliferation, apoptosis, invasion and metastasis (14). Evidence has emerged regarding the role of miR-21 in the regulation of drug resistance (15)(16)(17) and miR-21 overexpression is associated with the development of gefitinib resistance in NSCLC (18). To determine the involvement of miR-21 in exosome-mediated gefitinib resistance, RT-qPCR was performed to measure the expression of miR-21 in H827 cells.…”

Section: Exosomes Contribute To Gefitinib Resistance In Nsclc H827smentioning

confidence: 99%

Exosome‑mediated gefitinib resistance in lung cancer HCC827 cells via delivery of miR‑21

Jing

Qin

et al. 2018

Oncol Lett

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Abstract. Acquired resistance to gefitinib remains a major challenge in cancer treatment. In the present study, the effect of exosomes on the transmission of gefitinib resistance from gefitinib-resistant HCC827 lung cancer cells (H827R) to their gefitinib-sensitive counterparts and the potential underlying mechanisms by which this occurs was investigated. Exosomes were obtained from the cell supernatant using ultracentrifugation and the ExoQuick-TC exosome precipitation solution. Drug resistance was assessed by flow cytometry, apoptosis assays and cell counting kit-8 assays. The expression of microRNA (miR)-21 was analyzed by reverse transcription-quantitative polymerase chain reaction. Exosomes released by H827R cells (R/exo) may decrease the sensitivity of the human NSCLC HCC827 cell line to gefitinib. The results indicated that miR-21 expression was increased in R/exo and R/exo-treated H827S cells. However, miR-21 inhibition abrogated exosome-mediated drug resistance. Phosphorylated-protein kinase B (p-Akt), which is downstream of miR-21, was downregulated following gefitinib treatment; however, R/exo pretreatment elevated p-Akt levels and promoted the activation of Akt. By contrast, miR-21 inhibition reduced p-Akt expression. Therefore, the induction of miR-21 via exosomes and the activation of Akt may be mechanisms by which exosomes mediate the transfer of drug resistance.

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MiR-21 overexpression is associated with acquired resistance of EGFR-TKI in non-small cell lung cancer

Cited by 157 publications

References 46 publications

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

Emerging role of microRNA-21 in cancer

Exosome‑mediated gefitinib resistance in lung cancer HCC827 cells via delivery of miR‑21

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