Doxorubicin-induced novel circRNA_0004674 facilitates osteosarcoma progression and chemoresistance by upregulating MCL1 through miR-142-5p

Accumulating evidence has shown that circular RNA (circRNA) dysregulation is involved in various types of cancer, including osteosarcoma (OS). Nevertheless, the role and mechanism of circRNAs in OS progression and chemoresistance remain elusive. We found that a novel doxorubicin-induced circular RNA...

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Published in:Cell death discovery 2021-10, Vol.7 (1), p.309-309, Article 309
Main Authors: Ma, Xiao-Long, Zhan, Tai-Cheng, Hu, Jian-Ping, Zhang, Chun-Lin, Zhu, Kun-Peng
Format: Article
Language:English
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692/699/67/1344
692/699/67/1798
Apoptosis
Bcl-2 protein
Binding sites
Biochemistry
Bioinformatics
Biomedical and Life Sciences
Bone cancer
Cell Biology
Cell cycle
Cell Cycle Analysis
Cell migration
Chemoresistance
Circular RNA
Doxorubicin
Gene expression
Life Sciences
Mcl-1 protein
Osteosarcoma
Post-transcription
Sarcoma
Stem Cells
Transcriptomes
Tumors
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Summary:Accumulating evidence has shown that circular RNA (circRNA) dysregulation is involved in various types of cancer, including osteosarcoma (OS). Nevertheless, the role and mechanism of circRNAs in OS progression and chemoresistance remain elusive. We found that a novel doxorubicin-induced circular RNA, hsa_circ_0004674, screened by whole total transcriptome RNA sequencing in our previous study, was upregulated in OS chemoresistant cell lines and tissues and also connected with patients’ poor prognosis. Circ_0004674 knockdown remarkably suppressed OS cell chemoresistance, proliferation, migration, invasion, OS tumor growth, and enhanced cell cycle arrest and apoptosis in vitro and in vivo through control the expression of the antiapoptotic protein MCL1, a member of the Bcl-2 gene family. Further online bioinformatics analysis revealed that miR-142-5p had potential binding sites that can bind circ_0004674 and the 3′UTR of MCL1 mRNA. Moreover, the expression and function of miR-142-5p were conversely correlated with circ_0004674 in vitro. RIP, pull-down, luciferase assay, and RNA FISH demonstrated that circ_0004674 could compete with MCL1 for miR-142-5p binding to counteract miR-142-5p-mediated repression of MCL1 at the post-transcriptional level. To sum up, our study sheds light on the critical role of the oncogenic circ_0004674/miR-142-5p/MCL1 axis in OS progression and chemoresistance, providing a novel potential target for OS therapy.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-021-00694-8