miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting <i>CDKN1C</i>, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs
Colorectal cancer (CRC) is the third most common malignant tumor in the world and the second leading cause of cancer death. Multidrug resistance (MDR) has become a major obstacle in the clinical treatment of CRC. The clear molecular mechanism of MDR is complex, and miRNAs play an important role in d...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/13/3323 |
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| author | Fangqing Zhao Zhongmin Yang Xiaofan Gu Lixing Feng Mingshi Xu Xiongwen Zhang |
| author_facet | Fangqing Zhao Zhongmin Yang Xiaofan Gu Lixing Feng Mingshi Xu Xiongwen Zhang |
| author_sort | Fangqing Zhao |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is the third most common malignant tumor in the world and the second leading cause of cancer death. Multidrug resistance (MDR) has become a major obstacle in the clinical treatment of CRC. The clear molecular mechanism of MDR is complex, and miRNAs play an important role in drug resistance. This study used small RNAomic screens to analyze the expression profiles of miRNAs in CRC HCT8 cell line and its chemoresistant counterpart HCT8/T cell line. It was found that miR-92b-3p was highly expressed in HCT8/T cells. Knockdown of miR-92b-3p reversed the resistance of MDR HCT8/T cells to chemotherapeutic drugs in vitro and in vivo. Paclitaxel (PTX, a chemotherapy medication) could stimulate CRC cells to up-regulate miR-92b-3p expression and conferred cellular resistance to chemotherapeutic drugs. In studies on downstream molecules, results suggested that miR-92b-3p directly targeted Cyclin Dependent Kinase Inhibitor 1C (<i>CDKN1C</i>, which encodes a cell cycle inhibitor p57Kip2) to inhibit its expression and regulate the sensitivity of CRC cells to chemotherapeutic drugs. Mechanism study revealed that the miR-92b-3p/<i>CDKN1C</i> axis exerted a regulatory effect on the sensitivity of CRC cells via the regulation of cell cycle and apoptosis. In conclusion, these findings showed that miR-92b-3p/<i>CDKN1C</i> was an important regulator in the development of drug resistance in CRC cells, suggesting its potential application in drug resistance prediction and treatment. |
| first_indexed | 2024-03-10T09:52:49Z |
| format | Article |
| id | doaj.art-650731e0d0a840efbd16c9dc3136ceba |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:52:49Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-650731e0d0a840efbd16c9dc3136ceba2023-11-22T02:36:07ZengMDPI AGCancers2072-66942021-07-011313332310.3390/cancers13133323miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting <i>CDKN1C</i>, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic DrugsFangqing Zhao0Zhongmin Yang1Xiaofan Gu2Lixing Feng3Mingshi Xu4Xiongwen Zhang5Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaColorectal cancer (CRC) is the third most common malignant tumor in the world and the second leading cause of cancer death. Multidrug resistance (MDR) has become a major obstacle in the clinical treatment of CRC. The clear molecular mechanism of MDR is complex, and miRNAs play an important role in drug resistance. This study used small RNAomic screens to analyze the expression profiles of miRNAs in CRC HCT8 cell line and its chemoresistant counterpart HCT8/T cell line. It was found that miR-92b-3p was highly expressed in HCT8/T cells. Knockdown of miR-92b-3p reversed the resistance of MDR HCT8/T cells to chemotherapeutic drugs in vitro and in vivo. Paclitaxel (PTX, a chemotherapy medication) could stimulate CRC cells to up-regulate miR-92b-3p expression and conferred cellular resistance to chemotherapeutic drugs. In studies on downstream molecules, results suggested that miR-92b-3p directly targeted Cyclin Dependent Kinase Inhibitor 1C (<i>CDKN1C</i>, which encodes a cell cycle inhibitor p57Kip2) to inhibit its expression and regulate the sensitivity of CRC cells to chemotherapeutic drugs. Mechanism study revealed that the miR-92b-3p/<i>CDKN1C</i> axis exerted a regulatory effect on the sensitivity of CRC cells via the regulation of cell cycle and apoptosis. In conclusion, these findings showed that miR-92b-3p/<i>CDKN1C</i> was an important regulator in the development of drug resistance in CRC cells, suggesting its potential application in drug resistance prediction and treatment.https://www.mdpi.com/2072-6694/13/13/3323miR-92b-3p<i>CDKN1C</i>cell cycleapoptosischemoresistancecolorectal cancer |
| spellingShingle | Fangqing Zhao Zhongmin Yang Xiaofan Gu Lixing Feng Mingshi Xu Xiongwen Zhang miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting <i>CDKN1C</i>, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs Cancers miR-92b-3p <i>CDKN1C</i> cell cycle apoptosis chemoresistance colorectal cancer |
| title | miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting <i>CDKN1C</i>, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs |
| title_full | miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting <i>CDKN1C</i>, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs |
| title_fullStr | miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting <i>CDKN1C</i>, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs |
| title_full_unstemmed | miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting <i>CDKN1C</i>, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs |
| title_short | miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting <i>CDKN1C</i>, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs |
| title_sort | mir 92b 3p regulates cell cycle and apoptosis by targeting i cdkn1c i thereby affecting the sensitivity of colorectal cancer cells to chemotherapeutic drugs |
| topic | miR-92b-3p <i>CDKN1C</i> cell cycle apoptosis chemoresistance colorectal cancer |
| url | https://www.mdpi.com/2072-6694/13/13/3323 |
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