Back to Search
Start Over
The regulatory effect of has-circ-0001146/miR-26a-5p/MNAT1 network on the proliferation and invasion of osteosarcoma.
- Source :
-
Bioscience reports [Biosci Rep] 2020 Jun 26; Vol. 40 (6). - Publication Year :
- 2020
-
Abstract
- 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.<br /> (© 2020 The Author(s).)
- Subjects :
- Animals
Apoptosis
Bone Neoplasms genetics
Bone Neoplasms pathology
Cell Cycle Proteins genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Mice, Inbred BALB C
Mice, Nude
MicroRNAs genetics
Neoplasm Invasiveness
Osteosarcoma genetics
Osteosarcoma pathology
RNA, Circular genetics
Signal Transduction
Transcription Factors genetics
Tumor Burden
Young Adult
Bone Neoplasms metabolism
Cell Cycle Proteins metabolism
MicroRNAs metabolism
Osteosarcoma metabolism
RNA, Circular metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4935
- Volume :
- 40
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Bioscience reports
- Publication Type :
- Academic Journal
- Accession number :
- 32453410
- Full Text :
- https://doi.org/10.1042/BSR20201232