The regulatory effect of has-circ-0001146/miR-26a-5p/MNAT1 network on the proliferation and invasion of osteosarcoma

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.

Circ_0081001 down-regulates miR-494-3p to enhance BACH1 expression and promotes osteosarcoma progression

“…Circ_0102049, for example, promotes OS progression via modulating miR-1304-5p/MDM2 axis [ 8 ]. Circ_0001146 represses miR-26a-5p expression and up-regulates MNAT1 expression in OS cells, hence impeding OS growth [ 9 ]. Reportedly, circ_0081001 expression is elevated in OS tissues, cell lines, as well as patients' serum; COX regression analysis indicates that circ_0081001 is an independent risk factor that predicts the poor prognosis of the patients with OS [ 10 ].…”

METTL1 Mediated m7G Modification Regulates Ferroptosis and Chemotherapy Resistance via Involvement of pri-miR-26a/FTH1 Axis in Osteosarcoma

“…Interestingly, by further analyzing of AlkAniline-Seq dates and validation studies, we revealed that METTL1 de ciency dramatically reduces the mature of miR-26a-5p via m 7 G methylation, which has been reported to act as a tumor suppressor in osteosarcoma 38,39 . METTL1-mediated m 7 G position has been identi ed to be essential for let-7e stem-loop equilibrium and thereby promotes its processing, which can further selectively regulate the translation of oncogenic mRNAs in hepatoma carcinoma cells 10 .…”

Alteration in the Expression of Circular Rnas and its association with the Development and Progression of Osteosarcoma, an Integrative Review with High Sensitivity Research

“…Circular RNAs have also been linked to a higher incidence of metastases, particularly in the lungs, as reported in the literature. C39 [ 48 ], C43 [ 49 ], and C36 [ 50 ] are some examples. Moreover, circRNAs have been associated with advanced Enneking/TNM stages of osteosarcoma, as it was seen with C51 [ 51 ], C17 [ 52 ], and C60 [ 40 ].…”