HOXB13 networking with ABCG1/EZH2/Slug mediates metastasis and confers resistance to cisplatin in lung adenocarcinoma patients

Zhan, Jun; Wang, Peng; Li, Shuai; Song, Jianguo; He, Huiying; Wang, Yunling; Liu, Zhaofei; Wang, Fan; Bai, Hua; Fang, Wei‐Gang; Du, Qingyou; Ye, Min; Chen, Zhijie; Wang, Jie; Zhang, Hongquan

doi:10.7150/thno.29463

Cited by 46 publications

(40 citation statements)

References 62 publications

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“…The genes marked in * bold in Table 2 and in Table S3 are those that met these 2 criteria. These genes were already suggested for consideration as prognostic biomarkers in previous studies (selected references are listed in Table S12 [ 34 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Differential Expression of HOX Genes in Multiple Cancers

Adato

Orenstein

Kopolovic

et al. 2020

Cancers

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Transcription factors encoded by Homeobox (HOX) genes play numerous key functions during early embryonic development and differentiation. Multiple reports have shown that mis-regulation of HOX gene expression plays key roles in the development of cancers. Their expression levels in cancers tend to differ based on tissue and tumor type. Here, we performed a comprehensive analysis comparing HOX gene expression in different cancer types, obtained from The Cancer Genome Atlas (TCGA), with matched healthy tissues, obtained from Genotype-Tissue Expression (GTEx). We identified and quantified differential expression patterns that confirmed previously identified expression changes and highlighted new differential expression signatures. We discovered differential expression patterns that are in line with patient survival data. This comprehensive and quantitative analysis provides a global picture of HOX genes’ differential expression patterns in different cancer types.

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Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Differential Expression of HOX Genes in Multiple Cancers

Adato

Orenstein

Kopolovic

et al. 2020

Cancers

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“…EZH2, a core subunit of polycomb repressive complex 2 (PRC2), plays a vital role in treatment resistance in NSCLC 18,19 . To determine whether EZH2 is associated with gefitinib resistance, we examined EZH2 expression in PC9 and PC9/GR cells.…”

Section: Casc9 Drives Gefitinib Resistance Via Increasing Ezh2 and Acmentioning

confidence: 99%

Long non-coding RNA CASC9 promotes gefitinib resistance in NSCLC by epigenetic repression of DUSP1

Chen

Cheng

et al. 2020

Cell Death Dis

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Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, has greatly affected clinical outcomes in non-small cell lung cancer (NSCLC) patients. The long noncoding RNAs (lncRNAs) are known to regulate tumorigenesis and cancer progression, but their contributions to NSCLC gefitinib resistance remain poorly understood. In this study, by analyzing the differentially expressed lncRNAs in gefitinib-resistant cells and gefitinib-sensitive cells in the National Institute of Health GEO dataset, we found that lncRNA CASC9 expression was upregulated, and this was also verified in resistant tissues. Gain and loss of function studies showed that CASC9 inhibition restored gefitinib sensitivity both in vitro and in vivo, whereas CASC9 overexpression promoted gefitinib resistance. Mechanistically, CASC9 repressed the tumor suppressor DUSP1 by recruiting histone methyltransferase EZH2, thereby increasing the resistance to gefitinib. Furthermore, ectopic expression of DUSP1 increased gefitinib sensitivity by inactivating the ERK pathway. Our results highlight the essential role of CASC9 in gefitinib resistance, suggesting that the CASC9/EZH2/DUSP1 axis might be a novel target for overcoming EGFR-TKI resistance in NSCLC.

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“…Tumor cells that are resistant to chemotherapy exhibit characteristics of malignant behavior, including high proliferative capability and potent antiapoptotic ability (8,9). Although studies on cisplatin resistance have been performed previously (10)(11)(12), the molecular mechanism underlying tumor drug resistance remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

miR‑140‑3p enhances cisplatin sensitivity and attenuates stem cell‑like properties through repressing Wnt/β‑catenin signaling in lung adenocarcinoma cells

Wang

Pan

et al. 2020

Exp Ther Med

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Lung adenocarcinoma (LUAD) is the most predominant subtype of non-small cell lung cancer (NSCLC) that is experiencing the fastest growth rate in incidence. Chemoresistance and the presence of cancer stem cells are considered to be the main obstacles preventing the successful treatment of patients with NSCLC, the molecular mechanism of which remains poorly understood. The present study aimed to investigate the effects of microRNA (miR)-140-3p on cisplatin sensitivity and stem cell-like properties of LUAD cells. Analysis of publicly available data demonstrated that miR-140-3p expression was downregulated in LUAD, and positively associated with the overall survival rate of patients. In addition, transfection with the miR-140-3p mimic reduced LUAD cell viability and induced apoptosis following treatment with cisplatin whilst decreasing stem cell-like properties. miR-140-3p overexpression was also found to attenuate cisplatin resistance and reduce stem cell-like properties in LUAD cells by suppressing Wnt/β-catenin signaling, all of which were reversed by the overexpression of β-catenin. Taken together, results of the present study suggest miR-140-3p to be an effective therapeutic strategy for patients with LUAD.

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HOXB13 networking with ABCG1/EZH2/Slug mediates metastasis and confers resistance to cisplatin in lung adenocarcinoma patients

Cited by 46 publications

References 62 publications

Quantitative Analysis of Differential Expression of HOX Genes in Multiple Cancers

Quantitative Analysis of Differential Expression of HOX Genes in Multiple Cancers

Long non-coding RNA CASC9 promotes gefitinib resistance in NSCLC by epigenetic repression of DUSP1

miR‑140‑3p enhances cisplatin sensitivity and attenuates stem cell‑like properties through repressing Wnt/β‑catenin signaling in lung adenocarcinoma cells

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