MicroRNA-221 Promotes Cell Proliferation and Inhibits Apoptosis in Osteosarcoma Cells by Directly Targeting FBXW11 and Regulating Wnt Signaling.

Abstract

BACKGROUND AND OBJECTIVES:

MicroRNAs play a crucial role in the progression of various cancers, and microRNA-221 (miR-221) has been observed to be significantly overexpressed in osteosarcoma (OS) cells. FBXW11, a vital F-box protein of the ubiquitin-proteasome system, mediates the proliferation and survival of cancer cells by targeting multiple substrates for degradation. FBXW11 inhibits OS growth and metastasis by antagonizing the β-catenin/Wnt signaling pathway. Therefore, we hypothesized that miR-221 targets FBXW11 to mediate Wnt signaling and promote OS proliferation.

METHODS:

In this study, we demonstrated the increased expression of miR-221 and FBXW11 in OS tissues and cell lines by real-time polymerase chain reaction (RT-PCR). Moreover, to elucidate the regulatory mechanism(s) of miR-221 and FBXW11 in progression, cell viability and apoptosis were analyzed by the MTT assay and flow cytometry, respectively.

RESULTS:

The results showed that the overexpression of miR-221 in OS cells dramatically promoted cell growth and cell cycle progression, and inhibited apoptosis, whereas miR-221 inhibitors conversely inhibited proliferation and promoted apoptosis in OS cells. The data also showed that FBXW11 directly targeted miR-221 and miR-221 regulated OS cell proliferation and apoptosis by binding to FBXW11. We further confirmed that miR-221 targeted FBXW11 to promote proliferation and inhibit apoptosis in OS cell lines by inhibiting Wnt signaling.

INTERPRETATION AND CONCLUSIONS:

Overall, our study revealed a functional mechanism for miR-221 in OS. Further studies will elucidate its role in the progression of OS and inhibiting miR-221 may represent a useful treatment strategy.

• Authors: Qingzhu Zhang, Xuelian Yin, Yi Zhang
• Journal: Archives of medical research (Arch Med Res) Vol. 52 Issue 2 Pg. 191-199 (02 2021) ISSN: 1873-5487 [Electronic] United States
• PMID: 33131925 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 IMSS. Published by Elsevier Inc. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• FBXW11 protein, human
• MIRN221 microRNA, human
• MicroRNAs
• beta-Transducin Repeat-Containing Proteins
• Ubiquitin-Protein Ligases

Topics

• Adolescent
• Adult
• Apoptosis (physiology)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Bone Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Child
• Disease Progression
• Female
• Humans
• Male
• MicroRNAs (biosynthesis, genetics, metabolism)
• Middle Aged
• Osteosarcoma (genetics, metabolism, pathology)
• Transfection
• Ubiquitin-Protein Ligases (biosynthesis, genetics, metabolism)
• Wnt Signaling Pathway
• Young Adult
• beta-Transducin Repeat-Containing Proteins (biosynthesis, genetics, metabolism)