دورية أكاديمية
Melatonin Sensitizes Hepatocellular Carcinoma Cells to Chemotherapy Through Long Non-Coding RNA RAD51-AS1-Mediated Suppression of DNA Repair
| العنوان: | Melatonin Sensitizes Hepatocellular Carcinoma Cells to Chemotherapy Through Long Non-Coding RNA RAD51-AS1-Mediated Suppression of DNA Repair |
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| المؤلفون: | Chin-Chuan Chen, Chi-Yuan Chen, Shu-Huei Wang, Chau-Ting Yeh, Shih-Chi Su, Shir-Hwa Ueng, Wen-Yu Chuang, Chuen Hsueh, Tong-Hong Wang |
| المصدر: | Cancers, Vol 10, Iss 9, p 320 (2018) |
| بيانات النشر: | MDPI AG, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | melatonin, hepatocellular carcinoma, DNA repair, lncRNA-RAD51-AS1, RAD51, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | DNA repair systems are abnormally active in most hepatocellular carcinoma (HCC) cells due to accumulated mutations, resulting in elevated DNA repair capacity and resistance to chemotherapy and radiotherapy. Thus, targeting DNA repair mechanisms is a common treatment approach in HCC to sensitize cancer cells to DNA damage. In this study, we examined the anti-HCC effects of melatonin and elucidated the regulatory mechanisms. The results of functional assays showed that in addition to inhibiting the proliferation, migration, and invasion abilities of HCC cells, melatonin suppressed their DNA repair capacity, thereby promoting the cytotoxicity of chemotherapy and radiotherapy. Whole-transcriptome and gain- and loss-of-function analyses revealed that melatonin induces expression of the long noncoding RNA RAD51-AS1, which binds to RAD51 mRNA to inhibit its translation, effectively decreasing the DNA repair capacity of HCC cells and increasing their sensitivity to chemotherapy and radiotherapy. Animal models further demonstrated that a combination of melatonin and the chemotherapeutic agent etoposide (VP16) can significantly enhance tumor growth inhibition compared with monotherapy. Our results show that melatonin is a potential adjuvant treatment for chemotherapy and radiotherapy in HCC. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2072-6694 10090320 |
| Relation: | http://www.mdpi.com/2072-6694/10/9/320; https://doaj.org/toc/2072-6694 |
| DOI: | 10.3390/cancers10090320 |
| URL الوصول: | https://doaj.org/article/e7656aa7744d499fb796824ad57374b0 |
| رقم الأكسشن: | edsdoj.7656aa7744d499fb796824ad57374b0 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20726694 10090320 |
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| DOI: | 10.3390/cancers10090320 |