Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cells
Background Treatments that target cancer stem cells play an important role in the controlling and eliminating of tumor initiation as well as in development, progression, and chemotherapy/radiotherapy resistance. In our previous study, we cultured and harvested human laryngeal cancer stem cells (CSCs...
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PeerJ Inc.
2017-05-01
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| Online Access: | https://peerj.com/articles/3233.pdf |
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| author | Ying Zhu Li-Yun Shi Yan-Min Lei Yan-Hong Bao Zhao-Yang Li Fei Ding Gui-Ting Zhu Qing-Qing Wang Chang-Xin Huang |
| author_facet | Ying Zhu Li-Yun Shi Yan-Min Lei Yan-Hong Bao Zhao-Yang Li Fei Ding Gui-Ting Zhu Qing-Qing Wang Chang-Xin Huang |
| author_sort | Ying Zhu |
| collection | DOAJ |
| description | Background Treatments that target cancer stem cells play an important role in the controlling and eliminating of tumor initiation as well as in development, progression, and chemotherapy/radiotherapy resistance. In our previous study, we cultured and harvested human laryngeal cancer stem cells (CSCs) and applied microRNA biochips to screen differentially expressed miRNAs that were related to radiation tolerance in irradiated human laryngeal CSCs. According to the predicted genes and pathways of differential miRNAs target, down-regulated expression of hsa-miR-138-2-3p under radiation was thought to play a key role in enhancing the radio-sensitivity in human laryngeal squamous cancer stem cells. Method To investigate the radiational enhancement of hsa-miR-138-2-3p, we transfected hsa-miR-138-2-3p mimics that were synthesized based on the sequences of hsa-miR-138-2-3p in vitrointo human laryngeal CSCs (Hep-2, M2e, and TU212 cell lines) to make hsa-miR-138-2-3p overexpressed, and the tumorous specialities of CSCs, like cell proliferation, invasion, apoptosis, cell cycle arrest, and DNA damage were evaluated by CCK-8 assay, clone formation assay, invasion assay, flow cytometry, and comet assay. Furthermore, we explored the signal transduction pathways that regulated the cancer stem cell initiation, development, invasion, apoptosis and cell cycle arrest, which were controlled by hsa-miR-138-2-3p. Result Overexpressed hsa-miR-138-2-3p played a key role in many anti-cancer biological processes in human laryngeal CSCs: (1) it decreased laryngeal CSCs proliferation and invasion in response to radiotherapy; (2) it increased the proportion of early and late apoptosis in laryngeal CSCs after radiation, raised G1 phase arrest in laryngeal CSCs after radiation, and decreased the proportion of S stage cells of cell cycle that were related to radio-resistance in laryngeal CSCs; (3) it down-regulated the expression of β-catenin in Wnt signal pathway that was related to the tolerance of laryngeal CSCs to radiotherapy; (4) it down-regulated the expression of YAP1 in Hippo signal pathway that regulated cell proliferation, invasion and apoptosis; (5) it up-regulated the expression of p38 and JNK1 in MAPK signal pathway that was concerned to radio-sensitivity. Conclusion In the present study, it was found that hsa-miR-138-2-3p regulated the Wnt/β-catenin pathways, the Hippo/YAP1 pathways, and the MAPK/p38/JNK1 pathways that were involved in cell proliferation, invasion, apoptosis, cell cycle arrest, radio-resistance and radio-sensitivity in laryngeal CSCs. These results will be useful for a better understanding of the cell biology of hsa-miR-138-2-3p in laryngeal CSCs, and for serving hsa-miR-138-2-3p as a promising biomarker and as a target for diagnosis and for novel anti-cancer therapies for laryngeal cancers. |
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| spelling | doaj.art-ad4801c21a1845189c9cdcd3720d01272023-12-03T10:55:33ZengPeerJ Inc.PeerJ2167-83592017-05-015e323310.7717/peerj.3233Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cellsYing Zhu0Li-Yun Shi1Yan-Min Lei2Yan-Hong Bao3Zhao-Yang Li4Fei Ding5Gui-Ting Zhu6Qing-Qing Wang7Chang-Xin Huang8First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Immunology, School of Medical and Life Science, Nanjing University of Chinese Medicine, Nanjing, ChinaSecond Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaSecond Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Oncology, Affiliated Hospital with Hangzhou Normal University School of Medicine, Hangzhou, ChinaDepartment of Oncology, Affiliated Hospital with Hangzhou Normal University School of Medicine, Hangzhou, ChinaDepartment of Oncology, Affiliated Hospital with Hangzhou Normal University School of Medicine, Hangzhou, ChinaInstitute of Immunology, Zhejiang University, Hangzhou, ChinaDepartment of Oncology, Affiliated Hospital with Hangzhou Normal University School of Medicine, Hangzhou, ChinaBackground Treatments that target cancer stem cells play an important role in the controlling and eliminating of tumor initiation as well as in development, progression, and chemotherapy/radiotherapy resistance. In our previous study, we cultured and harvested human laryngeal cancer stem cells (CSCs) and applied microRNA biochips to screen differentially expressed miRNAs that were related to radiation tolerance in irradiated human laryngeal CSCs. According to the predicted genes and pathways of differential miRNAs target, down-regulated expression of hsa-miR-138-2-3p under radiation was thought to play a key role in enhancing the radio-sensitivity in human laryngeal squamous cancer stem cells. Method To investigate the radiational enhancement of hsa-miR-138-2-3p, we transfected hsa-miR-138-2-3p mimics that were synthesized based on the sequences of hsa-miR-138-2-3p in vitrointo human laryngeal CSCs (Hep-2, M2e, and TU212 cell lines) to make hsa-miR-138-2-3p overexpressed, and the tumorous specialities of CSCs, like cell proliferation, invasion, apoptosis, cell cycle arrest, and DNA damage were evaluated by CCK-8 assay, clone formation assay, invasion assay, flow cytometry, and comet assay. Furthermore, we explored the signal transduction pathways that regulated the cancer stem cell initiation, development, invasion, apoptosis and cell cycle arrest, which were controlled by hsa-miR-138-2-3p. Result Overexpressed hsa-miR-138-2-3p played a key role in many anti-cancer biological processes in human laryngeal CSCs: (1) it decreased laryngeal CSCs proliferation and invasion in response to radiotherapy; (2) it increased the proportion of early and late apoptosis in laryngeal CSCs after radiation, raised G1 phase arrest in laryngeal CSCs after radiation, and decreased the proportion of S stage cells of cell cycle that were related to radio-resistance in laryngeal CSCs; (3) it down-regulated the expression of β-catenin in Wnt signal pathway that was related to the tolerance of laryngeal CSCs to radiotherapy; (4) it down-regulated the expression of YAP1 in Hippo signal pathway that regulated cell proliferation, invasion and apoptosis; (5) it up-regulated the expression of p38 and JNK1 in MAPK signal pathway that was concerned to radio-sensitivity. Conclusion In the present study, it was found that hsa-miR-138-2-3p regulated the Wnt/β-catenin pathways, the Hippo/YAP1 pathways, and the MAPK/p38/JNK1 pathways that were involved in cell proliferation, invasion, apoptosis, cell cycle arrest, radio-resistance and radio-sensitivity in laryngeal CSCs. These results will be useful for a better understanding of the cell biology of hsa-miR-138-2-3p in laryngeal CSCs, and for serving hsa-miR-138-2-3p as a promising biomarker and as a target for diagnosis and for novel anti-cancer therapies for laryngeal cancers.https://peerj.com/articles/3233.pdfRadio-sensitivityLaryngeal cancerCancer stem cellSignal pathwayhsa-mir-138-2-3p |
| spellingShingle | Ying Zhu Li-Yun Shi Yan-Min Lei Yan-Hong Bao Zhao-Yang Li Fei Ding Gui-Ting Zhu Qing-Qing Wang Chang-Xin Huang Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cells PeerJ Radio-sensitivity Laryngeal cancer Cancer stem cell Signal pathway hsa-mir-138-2-3p |
| title | Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cells |
| title_full | Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cells |
| title_fullStr | Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cells |
| title_full_unstemmed | Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cells |
| title_short | Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cells |
| title_sort | radiosensitization effect of hsa mir 138 2 3p on human laryngeal cancer stem cells |
| topic | Radio-sensitivity Laryngeal cancer Cancer stem cell Signal pathway hsa-mir-138-2-3p |
| url | https://peerj.com/articles/3233.pdf |
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