The novel hsa-miR-12528 regulates tumourigenesis and metastasis through hypo-phosphorylation of AKT cascade by targeting IGF-1R in human lung cancer

• Published in: Cell death & disease 2018-05, Vol.9 (5), p.493-14, Article 493
• Main Authors: Jeon, Seong Ho, Yoo, Jung Ki, Kim, Chang Min, Lim, Eun Su, Lee, So Jeong, Lee, Ji Min, Oh, Seung-Hun, Kim, Jin Kyeoung
• Format: Article
• Language: English
• Subjects: 13/109; 13/2; 13/31; 13/89; 13/95; 3' Untranslated Regions; 38/5; 42/41; 45/90; 96/95; A549 Cells; AKT protein; Animals; Antibodies; Apoptosis; Binding Sites; Biochemistry; Biomedical and Life Sciences; Carcinogenesis; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Biology; Cell Culture; Cell Cycle; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Immunology; Insulin; Insulin-like growth factors; Life Sciences; Lung cancer; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Metastases; Metastasis; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neoplasm Invasiveness; Neoplasm Metastasis; Non-small cell lung carcinoma; Phosphorylation; Post-transcription; Proto-Oncogene Proteins c-akt - metabolism; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; Signal Transduction; Therapeutic applications; Tumor cell lines; Tumorigenesis; Tumors
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-0535-8

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.