miR-150-5p Inhibits Non-Small-Cell Lung Cancer Metastasis and Recurrence by Targeting HMGA2 and β-Catenin Signaling
Dysregulated microRNAs (miRNAs) play crucial roles in the regulation of cancer stem cells (CSCs), and CSCs are closely associated with tumor initiation, metastasis, and recurrence. Here we found that miR-150-5p was significantly downregulated in CSCs of non-small-cell lung cancer (NSCLC) and its exp...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253119300903 |
| _version_ | 1811212992309624832 |
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| author | Fu-Qiang Dai Cheng-Run Li Xiao-Qing Fan Long Tan Ren-Tao Wang Hua Jin |
| author_facet | Fu-Qiang Dai Cheng-Run Li Xiao-Qing Fan Long Tan Ren-Tao Wang Hua Jin |
| author_sort | Fu-Qiang Dai |
| collection | DOAJ |
| description | Dysregulated microRNAs (miRNAs) play crucial roles in the regulation of cancer stem cells (CSCs), and CSCs are closely associated with tumor initiation, metastasis, and recurrence. Here we found that miR-150-5p was significantly downregulated in CSCs of non-small-cell lung cancer (NSCLC) and its expression level was negatively correlated with disease progression and poor survival in patients with NSCLC. Inhibition of miR-150-5p increased the CSC population and sphere formation of NSCLC cells in vitro and stimulated NSCLC cell tumorigenicity and metastatic colonization in vivo. In contrast, miR-150-5p overexpression potently inhibited sphere-formed NSCLC cell tumor formation, metastatic colonization, and recurrence in xenograft models. Furthermore, we identified that miR-150-5p significantly inhibited wingless (Wnt)-β-catenin signaling by simultaneously targeting glycogen synthase kinase 3 beta interacting protein (GSKIP) and β-catenin in NSCLC cells. miR-150-5p also targeted high mobility group AT-hook 2 (HMGA2), another regulator of CSCs, and Wnt-β-catenin signaling. The restoration of HMGA2 and β-catenin blocked miR-150-5p overexpression-induced inhibition of CSC traits in NSCLC cells. These findings suggest that miR-150-5p functions as a CSC suppressor and that overexpression of miR-150-5p may be a novel strategy to inhibit CSC-induced metastasis and recurrence in NSCLC. Keywords: miR-150-5p, cancer stem cell, metastasis, recurrence, NSCLC |
| first_indexed | 2024-04-12T05:38:39Z |
| format | Article |
| id | doaj.art-4d08c83c685f403385e629d9555d55fa |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-12T05:38:39Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-4d08c83c685f403385e629d9555d55fa2022-12-22T03:45:44ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-06-0116675685miR-150-5p Inhibits Non-Small-Cell Lung Cancer Metastasis and Recurrence by Targeting HMGA2 and β-Catenin SignalingFu-Qiang Dai0Cheng-Run Li1Xiao-Qing Fan2Long Tan3Ren-Tao Wang4Hua Jin5Department of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, ChinaDepartment of Thoracic Surgery, The General Hospital of Chinese People’s Liberation Army, Beijing 100853, ChinaDepartment of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, ChinaDepartment of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, ChinaDepartment of Respiratory, The General Hospital of Chinese People’s Liberation Army, Beijing 100853, China; Corresponding author: Ren-Tao Wang, MD, Department of Respiratory, The General Hospital of Chinese People’s Liberation Army, Beijing 100853, China.Department of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China; Corresponding author: Hua Jin, PhD, Department of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.Dysregulated microRNAs (miRNAs) play crucial roles in the regulation of cancer stem cells (CSCs), and CSCs are closely associated with tumor initiation, metastasis, and recurrence. Here we found that miR-150-5p was significantly downregulated in CSCs of non-small-cell lung cancer (NSCLC) and its expression level was negatively correlated with disease progression and poor survival in patients with NSCLC. Inhibition of miR-150-5p increased the CSC population and sphere formation of NSCLC cells in vitro and stimulated NSCLC cell tumorigenicity and metastatic colonization in vivo. In contrast, miR-150-5p overexpression potently inhibited sphere-formed NSCLC cell tumor formation, metastatic colonization, and recurrence in xenograft models. Furthermore, we identified that miR-150-5p significantly inhibited wingless (Wnt)-β-catenin signaling by simultaneously targeting glycogen synthase kinase 3 beta interacting protein (GSKIP) and β-catenin in NSCLC cells. miR-150-5p also targeted high mobility group AT-hook 2 (HMGA2), another regulator of CSCs, and Wnt-β-catenin signaling. The restoration of HMGA2 and β-catenin blocked miR-150-5p overexpression-induced inhibition of CSC traits in NSCLC cells. These findings suggest that miR-150-5p functions as a CSC suppressor and that overexpression of miR-150-5p may be a novel strategy to inhibit CSC-induced metastasis and recurrence in NSCLC. Keywords: miR-150-5p, cancer stem cell, metastasis, recurrence, NSCLChttp://www.sciencedirect.com/science/article/pii/S2162253119300903 |
| spellingShingle | Fu-Qiang Dai Cheng-Run Li Xiao-Qing Fan Long Tan Ren-Tao Wang Hua Jin miR-150-5p Inhibits Non-Small-Cell Lung Cancer Metastasis and Recurrence by Targeting HMGA2 and β-Catenin Signaling Molecular Therapy: Nucleic Acids |
| title | miR-150-5p Inhibits Non-Small-Cell Lung Cancer Metastasis and Recurrence by Targeting HMGA2 and β-Catenin Signaling |
| title_full | miR-150-5p Inhibits Non-Small-Cell Lung Cancer Metastasis and Recurrence by Targeting HMGA2 and β-Catenin Signaling |
| title_fullStr | miR-150-5p Inhibits Non-Small-Cell Lung Cancer Metastasis and Recurrence by Targeting HMGA2 and β-Catenin Signaling |
| title_full_unstemmed | miR-150-5p Inhibits Non-Small-Cell Lung Cancer Metastasis and Recurrence by Targeting HMGA2 and β-Catenin Signaling |
| title_short | miR-150-5p Inhibits Non-Small-Cell Lung Cancer Metastasis and Recurrence by Targeting HMGA2 and β-Catenin Signaling |
| title_sort | mir 150 5p inhibits non small cell lung cancer metastasis and recurrence by targeting hmga2 and β catenin signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119300903 |
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