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Long non-coding RNA LINC00504 regulates the Warburg effect in ovarian cancer through inhibition of miR-1244

Molecular and Cellular Biochemistry volume 464, pages 39–50 (2020)Cite this article

Abstract

Ovarian cancer (OC) is the most lethal gynecologic malignancy and long non-coding RNAs (lncRNAs) have been acknowledged as important regulators in human OC. This study aimed to investigate the function and underlying mechanisms of LINC00504 in OC. The expression levels of LINC00504 in human OC tissues and cell lines were investigated by qRT-PCR analysis. The OC cell proliferation, and apoptosis were evaluated by MTT assay, colony-formation assay, Caspase-3 activity assay, and nucleosome ELISA assay, respectively. The metabolic shift in OC cells was examined by aerobic glycolysis analysis. Dual-luciferase activity reporter assay and mRNA–miRNA pull-down assay were conducted to validate the interaction between LINC00504 and miR-1244. LINC00504 was upregulated in OC cell lines and specimens. Knockdown of LINC00504 inhibited cell proliferation, enhanced apoptosis, decreased glycolysis-related gene (PKM2, HK2, and PDK1) expression, and altered aerobic glycolysis in OC cells and vice versa. LINC00504 downregulated miR-1244 expression levels by acting as an endogenous sponge of miR-1244. Inhibition of miR-1244 diminished the effects of LINC00504 on OC cells. Our study shows that LINC00504 promotes OC cell progression and stimulates aerobic glycolysis by interacting with miR-1244, which indicates that LINC00504 might act as a promising therapeutic target for OC treatment.

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Author notes

  1. Ya Liu and Xiaocui He have contributed equally to this work.

Affiliations

  1. Department of Gynecology, Heze Municipal Hospital, No. 2888 Caozhou Road, Mudan District, Heze, 274000, Shandong, China

    Ya Liu & Dan Cao

  2. Department of Gynecology and Obstetrics, Heze Municipal Hospital, No. 2888 Caozhou Road, Mudan District, Heze, 274000, Shandong, China

    Xiaocui He & Yuli Chen

Authors
  1. Ya Liu
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  2. Xiaocui He
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  3. Yuli Chen
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  4. Dan Cao
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Correspondence to Dan Cao.

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The study protocol was approved by the Ethics Committee of Heze Municipal Hospital. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Liu, Y., He, X., Chen, Y. et al. Long non-coding RNA LINC00504 regulates the Warburg effect in ovarian cancer through inhibition of miR-1244. Mol Cell Biochem 464, 39–50 (2020). https://doi.org/10.1007/s11010-019-03647-z

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  • DOI: https://doi.org/10.1007/s11010-019-03647-z

Keywords

  • Ovarian cancer (OC)
  • Long non-coding RNAs (lncRNAs)
  • LINC00504
  • Aerobic glycolysis
  • miR-1244