Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/1061
Full metadata record
DC FieldValueLanguage
dc.contributor.authorSaxena, Sandeep-
dc.contributor.authorNagarajan, Perumal-
dc.contributor.authorKhan, Md. Muntaz-
dc.contributor.authorGhosh, Tanushree-
dc.contributor.authorKumar, Praveen-
dc.contributor.authorPriyanka, Priyanka-
dc.contributor.authorShekhar, Ritu-
dc.date.accessioned2020-07-22T09:28:16Z-
dc.date.available2020-07-22T09:28:16Z-
dc.date.issued2019-03-
dc.identifier.urihttp://hdl.handle.net/123456789/1061-
dc.description.abstractMicroRNAs of the miR-16 and miR-34 families have been reported to inhibit cell cycle progression, and their loss has been linked to oncogenic transformation. Utilizing a high-throughput, genome-wide screen for miRNAs and mRNAs that are differentially regulated in osteosarcoma (OS) cell lines, we report that miR-449a and miR-424, belonging to the miR-34 and miR-16 families, respectively, target the major S/G2 phase cyclin, cyclin A2 (CCNA2), in a bipartite manner. We found that the 3'-UTR of CCNA2 is recognized by miR-449a, whereas the CCNA2 coding region is targeted by miR-424. Of note, we observed loss of both miR-449a and miR-424 in OS, resulting in derepression of CCNA2 and appearance of aggressive cancer phenotypes. Ectopic expression of miR-449a and miR-424 significantly decreased cyclin A2 levels and inhibited proliferation rate, migratory potential, and colony-forming ability of OS cells. To further probe the roles of miR-449a and miR-424 in OS, we developed an OS mouse model by intraosseous injection of U2OS cells into the tibia bone of NOD-scid mice, which indicated that miR-449a and miR-424 co-expression suppresses tumor growth. On the basis of this discovery, we analyzed the gene expression of human OS biopsy samples, revealing that miR-449a and miR-424 are both down-regulated, whereas cyclin A2 is significantly up-regulated in these OS samples. In summary, the findings in our study highlight that cyclin A2 repression by miRNAs of the miR-16 and miR-34 families is lost in aggressive OS.en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc.en_US
dc.subjectCCNA2; bone cancer; cell cycle; cyclin; cyclin A2; microRNA (miRNA); non-coding RNA; oncogenesis; osteosarcoma (OS); posttranscriptional regulation; tumor suppressor gene.en_US
dc.titleThe microRNAs miR-449a and miR-424 suppress osteosarcoma by targeting cyclin A2 expressionen_US
dc.journalJ Biol Chem .en_US
dc.volumeno294en_US
dc.issueno12en_US
dc.pages4381-4400en_US
Appears in Collections:DNA Replication and Cell Cycle, Publications

Files in This Item:
File Description SizeFormat 
zbc4381(1).pdf7.41 MBAdobe PDFView/Open    Request a copy


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.