The regulatory effect of has-circ-0001146/miR-26a-5p/MNAT1 network on the proliferation and invasion of osteosarcoma
| Autor: | Deye Song, Guangxu He, Junjie Wang, Jun Huang, Wen-Zhao Li, Muliang Ding, Jiangdong Ni |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Bioinformatics analysis Protein subunit Biophysics Mice Nude Apoptosis Bone Neoplasms Cell Cycle Proteins Biology has-circ-0001146 Biochemistry Young Adult Cell Movement Cell Line Tumor osteosarcoma medicine Animals Humans Neoplasm Invasiveness Viability assay Molecular Biology Research Articles Cell Proliferation Cancer Messenger RNA Mice Inbred BALB C Kinase Network on miR-26a-5p Cell Biology RNA Circular medicine.disease Tumor Burden Gene Expression Regulation Neoplastic MicroRNAs Cancer research Osteosarcoma Female MNAT1 Signal Transduction Transcription Factors |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 |
| Popis: | Osteosarcoma is a malignant bone tumour with the lowest survival rates out of all paediatric cancers and is primarily diagnosed in children and adolescents. MNAT1 is a subunit in the cyclin-dependent kinase-activating kinase complex. Abnormal up-regulation of MNAT1 has been associated with the poor prognosis of multiple cancers. Bioinformatics analysis showed that has-circ-0001146 and miR-26a-5p were involved in the regulation of MNAT1 in osteosarcoma. The present study investigated the regulatory effects of has-circ-0001146 and miR-26a-5p on MNAT1 expression using luciferase reporter and RNA-pull down assays. The effects of the has-circ-0001146/miR26a-5p/Mnat1 network on the proliferation and invasion of osteosarcoma were evaluated by cell viability, apoptosis, migration, and invasion assays. Osteosarcoma tissues showed higher MNAT1 and has-circ-0001146 expression than adjacent normal tissues, although the expression of MNAT1 was not significantly up-regulated in sarcomas according to TCGA databases. As indicated by luciferase reporter and RNA-pull down assays, miR-26a-5p was able to bind to both has-circ-0001146 and MNAT1 mRNA. The depletion of has-circ-0001146 as well as the increase of miR-26a-5p decreased MNAT1 expression in osteosarcoma cells, while the reduction of miR-26a-5p was associated with increased MNAT1 expression. These data suggested that has-circ-0001146 promoted MNAT1 expression by competitively binding to miR-26a-5p with MNAT1 mRNA. The depletion of has-circ-0001146 or MNAT1 or the increase of miR-26a-5p inhibited osteosarcoma cell viability and invasion, and increased apoptosis. Reduction of miR-26a-5p conversely promoted osteosarcoma cell viability and invasion. The present study confirmed that has-circ-0001146 blocked miR-26a-5p targeting MNAT1 in osteosarcoma cells, thereby promoting the malignant behaviours of osteosarcoma cells. |
| Databáze: | OpenAIRE |
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