miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells
Although aberrant expression of miR-34a, an essential tumor suppressor miRNA, has been frequently observed in colon cancer (CCa), whether miR-34a can regulate CCa progression by modulating other facets of this malignancy (such as multidrug resistance, MDR) remains unknown. Here, we report for the fi...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2018/7498514 |
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| author | Yong Li Ping Gong Ji-xue Hou Wei Huang Xiao-ping Ma Yu-li Wang Jing Li Xiao-bin Cui Na Li |
| author_facet | Yong Li Ping Gong Ji-xue Hou Wei Huang Xiao-ping Ma Yu-li Wang Jing Li Xiao-bin Cui Na Li |
| author_sort | Yong Li |
| collection | DOAJ |
| description | Although aberrant expression of miR-34a, an essential tumor suppressor miRNA, has been frequently observed in colon cancer (CCa), whether miR-34a can regulate CCa progression by modulating other facets of this malignancy (such as multidrug resistance, MDR) remains unknown. Here, we report for the first time that miR-34a expression was significantly downregulated in clinical CCa samples from oxaliplatin-resistant patients and in experimentally established multidrug-resistant CCa cells. By using histoculture drug response assay, we further confirmed that clinical CCa samples with lower miR-34a expression appeared to be more resistant to chemotherapy. Functionally, ectopic expression of exogenous miR-34a resensitized multidrug-resistant HCT-8/OR cells to oxaliplatin treatment, whereas miR-34a inhibition augmented the oxaliplatin resistance in chemosensitive HCT-8 cells. Mechanistically, miR-34a positively regulated the mRNA stability of the ornithine decarboxylase antizyme 2 (OAZ2) by directly targeting its three prime untranslated region (3′UTR). Consequently, suppression of the expression of miR-34a/OAZ2 signaling by chemotherapeutic agents significantly enhanced the activation of MDR-associated ATP-binding cassette (ABC) transporters and antiapoptosis pathways, thus leading to MDR development in CCa cells. Collectively, our combined analysis reveals a critical role of miR-34a/OAZ2 cascade in conferring a proper cellular response to CCa chemotherapy. |
| format | Article |
| id | doaj-art-972ded52db424d94ab077092a637bf2b |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-972ded52db424d94ab077092a637bf2b2025-02-03T06:01:07ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/74985147498514miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer CellsYong Li0Ping Gong1Ji-xue Hou2Wei Huang3Xiao-ping Ma4Yu-li Wang5Jing Li6Xiao-bin Cui7Na Li8Department of Radiology, Suining Central Hospital, Suining, Sichuan Province 629000, ChinaDepartment of Medical Oncology, First Affiliated Hospital of Medical College of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, ChinaDepartment of General Surgery, 2nd Division, First Affiliated Hospital of Medical College of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, ChinaDepartment of Medical Oncology, First Affiliated Hospital of Medical College of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, ChinaDepartment of Medical Oncology, First Affiliated Hospital of Medical College of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, ChinaDepartment of Medical Oncology, First Affiliated Hospital of Medical College of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, ChinaDepartment of Medical Oncology, First Affiliated Hospital of Medical College of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, ChinaDepartment of Pathology, First Affiliated Hospital of Medical College of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, ChinaDepartment of Medical Oncology, First Affiliated Hospital of Medical College of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, ChinaAlthough aberrant expression of miR-34a, an essential tumor suppressor miRNA, has been frequently observed in colon cancer (CCa), whether miR-34a can regulate CCa progression by modulating other facets of this malignancy (such as multidrug resistance, MDR) remains unknown. Here, we report for the first time that miR-34a expression was significantly downregulated in clinical CCa samples from oxaliplatin-resistant patients and in experimentally established multidrug-resistant CCa cells. By using histoculture drug response assay, we further confirmed that clinical CCa samples with lower miR-34a expression appeared to be more resistant to chemotherapy. Functionally, ectopic expression of exogenous miR-34a resensitized multidrug-resistant HCT-8/OR cells to oxaliplatin treatment, whereas miR-34a inhibition augmented the oxaliplatin resistance in chemosensitive HCT-8 cells. Mechanistically, miR-34a positively regulated the mRNA stability of the ornithine decarboxylase antizyme 2 (OAZ2) by directly targeting its three prime untranslated region (3′UTR). Consequently, suppression of the expression of miR-34a/OAZ2 signaling by chemotherapeutic agents significantly enhanced the activation of MDR-associated ATP-binding cassette (ABC) transporters and antiapoptosis pathways, thus leading to MDR development in CCa cells. Collectively, our combined analysis reveals a critical role of miR-34a/OAZ2 cascade in conferring a proper cellular response to CCa chemotherapy.http://dx.doi.org/10.1155/2018/7498514 |
| spellingShingle | Yong Li Ping Gong Ji-xue Hou Wei Huang Xiao-ping Ma Yu-li Wang Jing Li Xiao-bin Cui Na Li miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells Journal of Immunology Research |
| title | miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells |
| title_full | miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells |
| title_fullStr | miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells |
| title_full_unstemmed | miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells |
| title_short | miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells |
| title_sort | mir 34a regulates multidrug resistance via positively modulating oaz2 signaling in colon cancer cells |
| url | http://dx.doi.org/10.1155/2018/7498514 |
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