Screening Circular RNAs Related to Acquired Gefitinib Resistance in Non-small Cell Lung Cancer Cell Lines

Wen, Chunjie; Xu, Guohai; He, Shuai; Huang, Yutang; Shi, Jingjing; Wu, Long‐Fei; Zhou, Hong‐Hao

doi:10.7150/jca.39783

Cited by 21 publications

(18 citation statements)

References 51 publications

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“…hsa_circ_0109320 was found to be associated with the efficacy of gefitinib in patients with non‐small cell lung cancer (Liu et al, 2019). circRNAs were verified to be differentially expressed between GR and ‐sensitive cancer cells, and showed that (Wen et al, 2020). In the present study, our findings suggested that circPSMC3 expression levels was declined in ESCC tissues and ESCC cell lines, especially in GR ESCC cells, which prompted us to further study the function and potential mechanism of circPSMC3 in the drug resistance of ESCC.…”

Section: Discussionmentioning

confidence: 99%

Restoration of circPSMC3 sensitizes gefitinib‐resistant esophageal squamous cell carcinoma cells to gefitinib by regulating miR‐10a‐5p/PTEN axis

Zhu

Cao

2020

Cell Biology International

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Circular RNAs (circRNAs) has been shown to play an important role in the progression of various cancers. However, the function and underlying mechanisms of circRNAs affecting chemotherapy resistance in esophageal squamous cell carcinoma (ESCC) remain largely unknown. In this study, we used gefitinib‐resistant (GR) ESCC cells to investigate the function of circPSMC3 and clarify the underlying mechanism in chemotherapy resistance in ESCC. The results suggested that circPSMC3 expression was downregulated, but miR‐10a‐5p was upregulated in ESCC tissues and cells, as well as in GR ESCC cells. CircPSMC3 overexpression increased the sensitivity of ESCC cells to gefitinib, as indicated by reduced half maximal inhibitory concentration value, increased apoptosis rate and cleaved caspase‐3 protein expression. CircPSMC3 directly interacted with miR‐10a‐5p and inhibited the expression of miR‐10a‐5p. Phosphatase and tensin homolog (PTEN) was a direct target of miR‐10a‐5p and circPSMC3 promoted PTEN expression via decreasing miR‐10a‐5p level. Moreover, the effect of circPSMC3 on resistance of GR ESCC cells to gefitinib was remarkably reduced by restoration of miR‐10a‐5p and downregultion of PTEN. Taken together, these observations suggested that upregulation of circPSMC3 overcame resistance of GR ESCC cells to gefitinib by modulating the miR‐10a‐5p/PTEN axis, which provide a new therapeutic strategy for overcoming gefitinib resistance in ESCC.

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Section: Discussionmentioning

confidence: 99%

Restoration of circPSMC3 sensitizes gefitinib‐resistant esophageal squamous cell carcinoma cells to gefitinib by regulating miR‐10a‐5p/PTEN axis

Zhu

Cao

2020

Cell Biology International

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“…There are activating mutations located in the tyrosine kinase domain of the EGFR gene, including a 19-exon deletion and a point mutation in the 21 exon L858R ( 31 – 33 ). These activating mutations make EGFR highly sensitive to EGFR-TKIs molecular targeted drugs, such as gefitinib and erlotinib, but patients also develop resistance to these drugs ( 34 – 36 ). Previous studies have shown that changes in lipid metabolism in cancer cells are associated with EGFR-TKI resistance ( 37 – 39 ), and the inhibition of intracellular lipid droplet synthesis can reverse the resistance of cancer cells to gefitinib ( 40 ).…”

Section: Introductionmentioning

confidence: 99%

Implications of lipid droplets in lung cancer: Associations with drug resistance (Review)

Jin

Yuan

2020

Oncol Lett

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Cancer cells usually show different metabolic patterns compared with healthy cells due to the reprogramming of metabolic processes. The process of lipid metabolism undergoes notable changes, leading to the accumulation of lipid droplets in cells. Additionally, this phenotype is considered an important marker of cancer cells. Lipid droplets are a highly dynamic type of organelle in the cell, which is composed of a neutral lipid core, a monolayer phospholipid membrane and lipid droplet-related proteins. Lipid droplets are involved in several biological processes, including cell proliferation, apoptosis, lipid metabolism, stress, immunity, signal transduction and protein trafficking. Epidermal growth factor receptor (EGFR)-activating mutations are currently the most effective therapeutic targets for non-small cell lung cancer. Several EGFR tyrosine kinase inhibitors (EGFR-TKIs) that target these mutations, including gefitinib, erlotinib, afatinib and osimertinib, have been widely used clinically. However, the development of acquired resistance has a major impact on the efficacy of these drugs. A number of previous studies have reported that the expression of lipid droplets in the tumor tissues of patients with lung cancer are elevated, whereas the association between elevated numbers of lipid droplets and drug resistance has received little attention. The present review describes the potential association between lipid droplets and drug resistance. Furthermore, the mechanisms and implications of lipid droplet accumulation in cancer cells are analyzed, as wells as the mechanism by which lipid droplets suppress endoplasmic reticulum stress and apoptosis, which are essential for the development and treatment of lung cancer. Contents

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“…An increasing amount of evidence has shown that circRNAs are involved in several physiological and pathological processes of tumor development and progression ( Song and Fu, 2019 ; Wang et al, 2019 ; Zhang et al, 2019a , b , c ; Bai et al, 2020 ; Zhang N. et al, 2020 ; Zhang S. J. et al, 2020 ). CircRNAs have also been shown to be involved in resistance to immunotherapy, targeted therapy, and chemotherapy ( Zhang et al, 2019b ; Wen et al, 2020 ; Li et al, 2021 ). In this study, we identified abnormal gene expression in LUAD with data from the GEO database.…”

Section: Discussionmentioning

confidence: 99%

Construction of a circRNA-Related Prognostic Risk Score Model for Predicting the Immune Landscape of Lung Adenocarcinoma

Wang

Zhang

2021

Front. Genet.

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The purpose of this study was to construct a circular RNA (circRNA)-related competing endogenous RNA (ceRNA) regulatory network and risk score model for lung adenocarcinoma (LUAD). The relationship of the risk score to immune landscape and sensitivity to chemotherapy and targeted therapy of LUAD was assessed. We downloaded mRNA and miRNA expression data, along with clinical information, from The Cancer Genome Atlas (TCGA) program, and circRNA expression data from the Gene Expression Omnibus (GEO) database and identified differently expressed circRNA (DEcircRNA), miRNA (DEmiRNA), and mRNA (DEmRNA) using R software. We then constructed the circRNA-related network using bioinformatics method. The risk score model was established by LASSO Cox regression analysis based on 10 hub genes. In addition, the risk score model was an independent predictor for overall survival (OS) in both the TCGA and CPTAC datasets. Patients in the high-risk group had shorter OS and disease-free survival (DFS) than those in the low-risk group and were more sensitive to chemotherapy and targeted therapy. The types of tumor-infiltrating immune cells were different in the high- and low-risk groups. Our data revealed that the circRNA-related risk score model is closely associated with the level of immune cell infiltration in the tumor and the effects of adjuvant treatment. This network may be useful in designing personalized treatments for LUAD patients.

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Screening Circular RNAs Related to Acquired Gefitinib Resistance in Non-small Cell Lung Cancer Cell Lines

Cited by 21 publications

References 51 publications

Restoration of circPSMC3 sensitizes gefitinib‐resistant esophageal squamous cell carcinoma cells to gefitinib by regulating miR‐10a‐5p/PTEN axis

Restoration of circPSMC3 sensitizes gefitinib‐resistant esophageal squamous cell carcinoma cells to gefitinib by regulating miR‐10a‐5p/PTEN axis

Implications of lipid droplets in lung cancer: Associations with drug resistance (Review)

Construction of a circRNA-Related Prognostic Risk Score Model for Predicting the Immune Landscape of Lung Adenocarcinoma

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