Journal
AMERICAN JOURNAL OF CANCER RESEARCH
Volume 12, Issue 7, Pages 3464-+Publisher
E-CENTURY PUBLISHING CORP
Keywords
Osteosarcoma; microRNA; miR-1297; tumor growth; cell proliferation; cell cycle; cyclin D2
Categories
Funding
- National Natural Science Foundation of China [81601931]
- Natural Science Foundation of Jiangsu Province [BK20150475]
- Guizhou Provincial Health Commission [gzwkj2023-381]
- Six One Projects for high-level health professionals in Jiangsu Province Top Talent Project [LGY2019089]
- Medical education collaborative innovation Fund of Jiangsu university [JDY2022001]
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The present study demonstrated that miR-1297 inhibited proliferation and tumor growth in osteosarcoma by directly targeting CCND2.
Cyclin D2 (CCND2) is abnormally overexpressed in many tumor types and has been associated with tumor cell proliferation. Although the important role of miR-1297 is well established, the molecular mechanism between CCND2 and miR-1297 in osteosarcoma (OS) has not been determined. In the present study, we found CCND2 was highly expressed in OS cells, and its downregulation suppressed cell proliferation, resulting in G1 phase cell cycle arrest. In contrast, miR-1297 was lowly expressed in OS compared to normal tissue. Several data platforms predicted that CCND2 was a target of miR-1297, which was validated by a dual-luciferase reporter assay that revealed miR-1297 could bind with CCND2-3'UTR. miR-1297 overexpression greatly inhibited CCND2 protein expression and exerted the same phenotypic effect as CCND2 downregulation in OS cells. Furthermore, miR-1297 inhibition could also be rescued by CCND2. Nude mice injected cells stable overexpressing miR-1297 OS cells showed lower size and tumor weight. Moreover, lower fluorescence activity recorded by in vivo imaging system and bone erosion revealed by microCT in the miR-1297 group demonstrated miR-1297 inhibited OS tumor growth via CCND2. Our findings demonstrated that miR-1297 can inhibit proliferation and tumor growth in OS by directly targeting CCND2, which indicates that miR-1297 may represent a novel therapeutic target for OS.
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