Targeting MALAT1 induces DNA damage and sensitize non-small cell lung cancer cells to cisplatin by repressing BRCA1
| العنوان: | Targeting MALAT1 induces DNA damage and sensitize non-small cell lung cancer cells to cisplatin by repressing BRCA1 |
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| المؤلفون: | Changxiu Lin, Chunhua Jin, Hengmin Han, Jinghua Huang, Zhengri Piao, Hai Dong, Dongchun Jin |
| المصدر: | Cancer Chemotherapy and Pharmacology. 86:663-672 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, DNA End-Joining Repair, Lung Neoplasms, DNA repair, DNA damage, LIG3, Toxicology, 03 medical and health sciences, 0302 clinical medicine, PARP1, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Antineoplastic Combined Chemotherapy Protocols, microRNA, medicine, Humans, Pharmacology (medical), RNA, Small Interfering, Pharmacology, Cisplatin, BRCA1 Protein, Chemistry, Computational Biology, Up-Regulation, respiratory tract diseases, Gene Expression Regulation, Neoplastic, Comet assay, MicroRNAs, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Cancer research, RNA, Long Noncoding, Homologous recombination, DNA Damage, medicine.drug |
| الوصف: | Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA which has been identified to be involved in alternative non-homologous end joining (A-NHEJ) pathways by binding with PARP1 and LIG3 in myeloma cells. This study aims to explore the roles of MALAT1 in DNA repair processes in non-small cell lung cancer (NSCLC). The interactions between MALAT1 and proteins were identified by co-immunoprecipitation and RNA pulldown. The interactions between MALAT1 and microRNAs (miRNA) were predicted by bioinformatics tools and confirmed by luciferase assay and RNA pulldown. The DNA damages were quantified by comet assay. The cell viability was examined by MTT assay and the cell apoptosis was determined by flow cytometry. MALAT1 is identified to be involved in A-NHEJ pathway in NSCLC cells. However, in LIG3-null cells where A-NHEJ pathway is inactivated, targeting MALAT1 still increases DNA damages, suggesting that MALAT1 participates in other DNA repair pathways. Subsequently, MALAT1 is identified to bind with miR-146a and miR-216b, which directly target the 3′UTR of BRCA1. MALAT1 is confirmed to functions as a competing endogenous RNA (ceRNA) absorbing miR-146a and miR-216b, upregulating BRCA1 expression and protecting Homologous Recombination (HR) pathway in NSCLC cells. Finally, overexpression MALAT1 protects NSCLC cells from the cytotoxic effect of cisplatin. While, targeting MALAT1 in NSCLC cells induces DNA damages by repressing HR pathway and sensitizes NSCLC cells to cisplatin which had the potential for NSCLC treatment. MALAT1 is involved in HR pathway by protecting BRCA1 and targeting MALAT1 induces DNA damages in NSCLC. |
| تدمد: | 1432-0843 0344-5704 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a517969cda1042642e3362e18669f00eTest https://doi.org/10.1007/s00280-020-04152-7Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....a517969cda1042642e3362e18669f00e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320843 03445704 |
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