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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2025 03

Page:

388-395

Research Field:

Publishing date:

Info

Title:

miR-29a-3p inhibits osteosarcoma cells stemness and its molecular mechanism

Author(s):

KUANG Jian¹; DONG Wengang²; DING Jiayun¹; LIU Jiong¹; LIU Wenyi¹; ZHOU Zhijian¹; LIU Jun¹

1.Southern Center for Diseases Control and Prevention,Guangdong Guangzhou 510630,China£»2.Department of Emergency Surgery,Shaanxi Provincial People's Hospital,Shaanxi Xi'an 710068,China.

Keywords:

osteosarcoma; tumor stem cells; miR-29a-3p; Wnt signal pathway

PACS:

R738.1

DOI:

10.3969/j.issn.1672-4992.2025.03.005

Abstract:

Objective:To study whether miR-29a-3p affects osteosarcoma cells stemness and explore its underlying molecular mechanism.Methods:Osteosarcoma stem cells were enriched and cultured on ultralow attachment Corning plates and grown in sphere media,real-time PCR assays were used to detect the level of miR-29a-3p in osteosarcoma cell lines and stem cells.Then,by regulating the expression of miR-29a-3p,its effects on the expression levels of osteosarcoma stemness markers,such as Nanog,Oct-4,Sox2,and clone formation capacities were detected.Online bioinformatics prediction through TargetScan website was performed to testify the targeting gene of miR-29a-3p,which was TRAF5,tumor necrosis factor receptor associated factor-5.Then,the targeting relationship between miR-29a-3p and TRAF5 was confirmed through dual luciferase reporter assays.And we also explored the effects of miR-29a-3p on TRAF5 expression on mRNA or protein level by real-time PCR,Western blotting experiments.Rescue experiments were also performed to verify that miR-29a-3p can regulate osteosarcoma stemness markers expression and clone formation capacities by targeting TRAF5.To further investigate whether Wnt/¦Â-catenin pathway participates in the above mentioned roles of miR-29a-3p,we inspected the nuclear accumulation of ¦Â-catenin and used TOPFlash reporter plasmids to examine the activation level of Wnt signal pathway.Finally,we detected the expression level of Wnt-related proteins,TCF-4,Pygo2 by Western blotting.Results:Real-time PCR results showed that miR-29a-3p was aberrantly downregulated in osteosarcoma cell lines and stem cells,and we also found miR-29a-3p could inhibit stemness markers expression and clone formation capacities of osteosarcoma stem cells.Bioinformatics prediction and molecular biology experiments demonstrated that miR-29a-3p could inhibit osteosarcoma stem cells stemness through targeting TRAF5.Further studies showed miR-29a-3p inhibition could promote nuclear accumulation of ¦Â-catenin,TCF/LEF transcription level and upregulation of Wnt-related proteins,TCF-4,Pygo2.However,simultaneously inhibition of miR-29a-3p and TRAF5 could partly reverse the above phenomenon.Conclusion:miR-29a-3p could repress the stemness of osteosarcoma stem cells through Wnt/¦Â-catenin pathway by targeting TRAF5.

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