Cancer-Specific Energy Metabolism in Rhabdomyosarcoma Cells Is Regulated by MicroRNA

Nobuhiko Sugito, Kohei Taniguchi, Yuki Kuranaga, Maki Ohishi, Tomoyoshi Soga, Yuko Ito, Mitsuru Miyachi, Ken Kikuchi, Hajime Hosoi, Yukihiro Akao

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma and is most frequently found in children. In RMS, there are two major subtypes, that is, embryonal RMS and alveolar RMS (ARMS). ARMS has exclusively the worse prognosis and is caused by formation of the chimeric PAX3-FOXO1 gene. Regarding cancer, the Warburg effect is known as a feature of cancer-specific metabolism. Polypyrimidine tract-binding protein 1 (PTBP1), a splicer of pyruvate kinase muscle (PKM) mRNA, is a positive regulator of cancer-specific energy metabolism. We investigated the expression and effects of muscle-specific miR-1 and miR-133b on RMS cells (RD, KYM-1, Rh30, and Rh41) from the view of energy metabolism and regulation of the chimeric gene. As a result, downregulated miR-1 and miR-133b/upregulated PTBP1 were found in RMS cell lines as well as in RMS clinical cases. Ectopic expression of either miR in both types of RMS cells induced autophagic cell death through silencing of PTBP1. Interestingly, we validated that miR-133b also knock downed PAX3-FOXO1. Moreover, we found that PAX3-FOXO1 positively regulated the PKM2-dominant expression through enhanced expression of PTBP1. These findings suggest that the miR-1 and miR-133b/PTBP1 axis and miR-133b/PAX3-FOXO1/PTBP1 axis contributed to the maintenance of cancer-specific energy metabolism.

Original languageEnglish
Pages (from-to)365-377
Number of pages13
JournalNucleic Acid Therapeutics
Volume27
Issue number6
DOIs
Publication statusPublished - 2017 Dec 1

Fingerprint

Polypyrimidine Tract-Binding Protein
Rhabdomyosarcoma
MicroRNAs
Energy Metabolism
Neoplasms
Muscle
Genes
Alveolar Rhabdomyosarcoma
Embryonal Rhabdomyosarcoma
Muscles
Pyruvate Kinase
Autophagy
Cell death
Metabolism
Sarcoma
Down-Regulation
Cells
Maintenance
Tissue
Cell Line

Keywords

  • microRNA
  • PAX3-FOXO1
  • PTBP1
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

Cite this

Cancer-Specific Energy Metabolism in Rhabdomyosarcoma Cells Is Regulated by MicroRNA. / Sugito, Nobuhiko; Taniguchi, Kohei; Kuranaga, Yuki; Ohishi, Maki; Soga, Tomoyoshi; Ito, Yuko; Miyachi, Mitsuru; Kikuchi, Ken; Hosoi, Hajime; Akao, Yukihiro.

In: Nucleic Acid Therapeutics, Vol. 27, No. 6, 01.12.2017, p. 365-377.

Research output: Contribution to journalArticle

Sugito, N, Taniguchi, K, Kuranaga, Y, Ohishi, M, Soga, T, Ito, Y, Miyachi, M, Kikuchi, K, Hosoi, H & Akao, Y 2017, 'Cancer-Specific Energy Metabolism in Rhabdomyosarcoma Cells Is Regulated by MicroRNA', Nucleic Acid Therapeutics, vol. 27, no. 6, pp. 365-377. https://doi.org/10.1089/nat.2017.0673
Sugito, Nobuhiko ; Taniguchi, Kohei ; Kuranaga, Yuki ; Ohishi, Maki ; Soga, Tomoyoshi ; Ito, Yuko ; Miyachi, Mitsuru ; Kikuchi, Ken ; Hosoi, Hajime ; Akao, Yukihiro. / Cancer-Specific Energy Metabolism in Rhabdomyosarcoma Cells Is Regulated by MicroRNA. In: Nucleic Acid Therapeutics. 2017 ; Vol. 27, No. 6. pp. 365-377.
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AU - Hosoi, Hajime

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