The novel hsa-miR-12528 regulates tumourigenesis and metastasis through hypo-phosphorylation of AKT cascade by targeting IGF-1R in human lung cancer
| العنوان: | The novel hsa-miR-12528 regulates tumourigenesis and metastasis through hypo-phosphorylation of AKT cascade by targeting IGF-1R in human lung cancer |
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| المؤلفون: | Jin Kyeoung Kim, Seung-Hun Oh, So Jeong Lee, Eun Su Lim, Ji Min Lee, Jung Ki Yoo, Seong Ho Jeon, Chang Min Kim |
| المصدر: | Cell Death & Disease Cell Death and Disease, Vol 9, Iss 5, Pp 1-14 (2018) |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Lung Neoplasms, Immunology, Mice, Nude, Apoptosis, Biology, medicine.disease_cause, Article, Receptor, IGF Type 1, Metastasis, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cell Movement, Carcinoma, Non-Small-Cell Lung, microRNA, medicine, Animals, Humans, Neoplasm Invasiveness, lcsh:QH573-671, Neoplasm Metastasis, Phosphorylation, Lung cancer, 3' Untranslated Regions, Protein kinase B, Carcinogen, Cell Proliferation, A549 cell, Mice, Inbred BALB C, Binding Sites, lcsh:Cytology, Cell Cycle, Cell Biology, medicine.disease, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, A549 Cells, 030220 oncology & carcinogenesis, Cancer research, Carcinogenesis, Proto-Oncogene Proteins c-akt, Signal Transduction |
| الوصف: | Lung cancer cases are increasing yearly; however, few novel therapeutic strategies for treating this disease have been developed. Here the dysregulation between microRNAs and oncogenes or tumour-suppressor genes forms a close connection-loop to the development or progression in human lung carcinogenesis. That is, the relationship between microRNAs and carcinogenic mechanism may find the critical clue to improve the treatment efficacy. Accordingly, we identified and characterised a novel microRNA, hsa-miR-12528, in A549 cells. The miR-12528 expression was aberrantly downregulated in cancer cell lines and in the patient tissues derived from human non-small cell lung cancer. In addition, we found that miR-12528 post-transcriptionally controls the translation of the insulin-like growth factor 1 receptor (IGF-1R) gene by directly targeting the 3′-untranslated region of IGF-1R mRNA. Notably, the IGF-1R gene is elevated in the majority of cancers and may be an attractive therapeutic target for anticancer therapy because elevated IGF-1R mediates the signalling amplification of a major oncogenic pathway in neoplasia. In A549 cells, miR-12528 overexpression epigenetically altered the downstream phosphorylation of the primary IGF-1R networks, negatively regulated proliferation, apoptosis and migratory activity, and consequently inhibited tumourigenesis and metastasis in vivo. Therefore, our discovery of hsa-miR-12528 may be able to be applied to the development of molecular-target therapeutic strategies and diagnosis-specific biomarkers for human lung cancer. |
| تدمد: | 2041-4889 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b7aa3bb06313115b9a6d3abf73789593 https://doi.org/10.1038/s41419-018-0535-8 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b7aa3bb06313115b9a6d3abf73789593 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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