Exosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A
Guoqing Gu,1,* Chenxi Hu,1,* Kaiyuan Hui,1 Huiqin Zhang,1 Ting Chen,1 Xin Zhang,2 Xiaodong Jiang1 1Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, 222000, People’s Republic of China; 2Lianyungang Clinical College of Nanj...
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oai:doaj.org-article:40ea827694da4063ae886ee12768c4382021-12-02T17:38:06ZExosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A1178-2013https://doaj.org/article/40ea827694da4063ae886ee12768c4382021-09-01T00:00:00Zhttps://www.dovepress.com/exosomal-mir-136-5p-derived-from-anlotinib-resistant-nsclc-cells-confe-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Guoqing Gu,1,* Chenxi Hu,1,* Kaiyuan Hui,1 Huiqin Zhang,1 Ting Chen,1 Xin Zhang,2 Xiaodong Jiang1 1Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, 222000, People’s Republic of China; 2Lianyungang Clinical College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong JiangDepartment of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Haizhou District, Lianyungang, Jiangsu, 222000, People’s Republic of ChinaEmail jxdpaper@163.comBackground: Anlotinib resistance is a challenge for advanced non-small cell lung cancer (NSCLC). Understanding the underlying mechanisms against anlotinib resistance is of great importance to improve prognosis and treatment of patients with advanced NSCLC.Methods: RT-qPCR assay was used to assess the level of miR-136-5p in anlotinib-resistant NSCLC cells and exosomes derived from anlotinib-resistant NSCLC cells. In addition, miR-136-5p level in tumor tissues from patients who exhibited a poor response to anlotinib therapy and patients who were therapy naïve or patients who exhibited a positive response to anlotinib therapy was detected by RT-qPCR assay.Results: In this study, we found that high levels of plasma exosomal miR-136-5p is correlated with clinically poor anlotinib response. In addition, anlotinib-resistant NSCLC cells promoted parental NSCLC cell proliferation via transferring functional miR-136-5p from anlotinib-resistant NSCLC cells to parental NSCLC cells via exosomes. Moreover, exosomal miR-136-5p could endow NSCLC cells with anlotinib resistance by targeting PPP2R2A, leading to the activation of Akt pathway. Furthermore, miR-136-5p antagomir packaging into anlotinib-resistant NSCLC cell-derived exosomes functionally restored NSCLC cell anlotinib sensitivity in vitro. Animal studies showed that A549/anlotinib cell-derived exosomal miR-136-5p agomir promoted A549 cell anlotinib resistance in vivo.Conclusion: Collectively, these findings indicated that anlotinib-resistant NSCLC cell-derived exosomal miR-136-5p confers anlotinib resistance in NSCLC cells by targeting PPP2R2A, indicating miR-136-5p may act as a potential biomarker for anlotinib response in NSCLC.Keywords: advanced non-small cell lung cancer, anlotinib resistance, exosome, microRNAGu GHu CHui KZhang HChen TZhang XJiang XDove Medical Pressarticleadvanced non-small cell lung canceranlotinib resistanceexosomemicrorna.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 6329-6343 (2021) |
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advanced non-small cell lung cancer anlotinib resistance exosome microrna. Medicine (General) R5-920 |
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advanced non-small cell lung cancer anlotinib resistance exosome microrna. Medicine (General) R5-920 Gu G Hu C Hui K Zhang H Chen T Zhang X Jiang X Exosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A |
| description |
Guoqing Gu,1,* Chenxi Hu,1,* Kaiyuan Hui,1 Huiqin Zhang,1 Ting Chen,1 Xin Zhang,2 Xiaodong Jiang1 1Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, 222000, People’s Republic of China; 2Lianyungang Clinical College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong JiangDepartment of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Haizhou District, Lianyungang, Jiangsu, 222000, People’s Republic of ChinaEmail jxdpaper@163.comBackground: Anlotinib resistance is a challenge for advanced non-small cell lung cancer (NSCLC). Understanding the underlying mechanisms against anlotinib resistance is of great importance to improve prognosis and treatment of patients with advanced NSCLC.Methods: RT-qPCR assay was used to assess the level of miR-136-5p in anlotinib-resistant NSCLC cells and exosomes derived from anlotinib-resistant NSCLC cells. In addition, miR-136-5p level in tumor tissues from patients who exhibited a poor response to anlotinib therapy and patients who were therapy naïve or patients who exhibited a positive response to anlotinib therapy was detected by RT-qPCR assay.Results: In this study, we found that high levels of plasma exosomal miR-136-5p is correlated with clinically poor anlotinib response. In addition, anlotinib-resistant NSCLC cells promoted parental NSCLC cell proliferation via transferring functional miR-136-5p from anlotinib-resistant NSCLC cells to parental NSCLC cells via exosomes. Moreover, exosomal miR-136-5p could endow NSCLC cells with anlotinib resistance by targeting PPP2R2A, leading to the activation of Akt pathway. Furthermore, miR-136-5p antagomir packaging into anlotinib-resistant NSCLC cell-derived exosomes functionally restored NSCLC cell anlotinib sensitivity in vitro. Animal studies showed that A549/anlotinib cell-derived exosomal miR-136-5p agomir promoted A549 cell anlotinib resistance in vivo.Conclusion: Collectively, these findings indicated that anlotinib-resistant NSCLC cell-derived exosomal miR-136-5p confers anlotinib resistance in NSCLC cells by targeting PPP2R2A, indicating miR-136-5p may act as a potential biomarker for anlotinib response in NSCLC.Keywords: advanced non-small cell lung cancer, anlotinib resistance, exosome, microRNA |
| format |
article |
| author |
Gu G Hu C Hui K Zhang H Chen T Zhang X Jiang X |
| author_facet |
Gu G Hu C Hui K Zhang H Chen T Zhang X Jiang X |
| author_sort |
Gu G |
| title |
Exosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A |
| title_short |
Exosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A |
| title_full |
Exosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A |
| title_fullStr |
Exosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A |
| title_full_unstemmed |
Exosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A |
| title_sort |
exosomal mir-136-5p derived from anlotinib-resistant nsclc cells confers anlotinib resistance in non-small cell lung cancer through targeting ppp2r2a |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/40ea827694da4063ae886ee12768c438 |
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