Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr;13(4):8038-8050.
doi: 10.1080/21655979.2022.2051785.

Fat mass and obesity associated (FTO)-mediated N6-methyladenosine modification of Krüppel-like factor 3 (KLF3) promotes osteosarcoma progression

Hong-Jian Shan  1   2 , Wen-Xiang Gu  1 , Gang Duan  3 , Hong-Liang Chen  1
Affiliations

Fat mass and obesity associated (FTO)-mediated N6-methyladenosine modification of Krüppel-like factor 3 (KLF3) promotes osteosarcoma progression

Hong-Jian Shan et al. Bioengineered. 2022 Apr.

Abstract

ARSTRACTN6-methyladenosine (m6A) methylation is the most common and abundant methylation modification of eukaryotic mRNAs, which is involved in tumor initiation and progression. The study aims to explore the potential role and the regulatory mechanism of fat mass and obesity associated (FTO) in osteosarcoma (OS) progression. In this study, we detected the expressions of Krüppel-like factor 3 (KLF3) in OS cells and tissues and found that the mRNA and protein levels of KLF3 were increased in OS cells and tissues and significantly related to tumor size, metastasis, and TNM stage and poor prognosis of OS patients. FTO promoted the proliferation and invasion and suppressed apoptosis of OS cells through cell experiments in vitro. Further mechanism dissection revealed that FTO and YTHDF2 enforced the decay of KLF3 mRNA and decreased its expression. FTO-mediated mRNA demethylation inhibited KLF3 expression in the YTHDF2-dependent manner. Moreover, KLF3 overexpression abrogated FTO-induced oncogenic effects on the proliferation and invasion of OS cells. Overall, our findings showed that FTO-mediated m6A modification of KLF3 promoted OS progression, which may provide a therapeutic target for OS.

Keywords: FTO; KLF3; m6A methylation; osteosarcoma.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

None
Graphical abstract
Figure 1.
Figure 1.
FTO is increased in OS tissues.
Figure 2.
Figure 2.
FTO promotes proliferation, invasion of OS cells and inhibits cell apoptosis.
Figure 3.
Figure 3.
FTO regulates KLF3 expression in an m6A-dependent manner in OS cells.
Figure 4.
Figure 4.
KLF3 impairs the FTO-induced proliferation and invasion of OS cells.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Lu KH, Lin RC, Yang JS, et al. Molecular and cellular mechanisms of melatonin in osteosarcoma. Cells. 2019;8(12):1618. - PMC - PubMed
    1. Bielack SS, Kempf-Bielack B, Delling G, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002;20(3):776–790. - PubMed
    1. Mialou V, Philip T, Kalifa C, et al. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome–the French pediatric experience. Cancer. 2005;104(5):1100–1109. - PubMed
    1. Harrison DJ, Geller DS, Gill JD, et al. Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther. 2018;18(1):39–50. - PubMed
    1. Huo FC, Zhu ZM, Pei DS.. N(6) -methyladenosine (m(6) A) RNA modification in human cancer. Cell Prolif. 2020;53(11):e12921. - PMC - PubMed

Publication types

MeSH terms