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Knock-down of LncRNA-XIST induced glioma cell death and inhibited tumorigenesis by regulating miR-137/SLC1A5 axis-mediated ROS production

Abstract

Glioma seriously degrades the life quality of afflicted human beings. Uncovering the underlying mechanisms of the pathogenesis of glioma is a step needed to help provide new therapeutic agents for clinical treatments. This study aimed to explore the role of the LncRNA-XIST/miR-137/SLC1A5 axis in influencing the regulation of development of glioma. Our results indicated that LncRNA-XIST and SLC1A5 were expressed at high levels and contrastingly indicated that miR-137 was expressed at low levels in glioma cells when compared results for normal human astrocytes (NHAs). Further, our findings indicated that downregulation of LncRNA-XIST promoted both glioma cell apoptosis and ROS production as well as inhibited cell proliferation. All these effects were reversed by treating cells with ROS scavenger N-acetyl-L-Cysteine (NAC). In addition, inducing the knock-down of LncRNA-XIST was found to have decreased the expression levels of SLC1A5 by sponging miR-137 in glioma cells. Notably, both the knocking down of miR-137 and/or induced overexpression of SLC1A5 abrogated the effects of downregulated LncRNA-XIST on glioma cell proliferation, apoptosis, and ROS production. Furthermore, in vivo experiments validated that LncRNA-XIST deficiency inhibited tumorigenesis of glioma cells in examinations of nude mice and these effects were reversible by way of either downregulating miR-137 or upregulating SLC1A5. Taken together, knocking down LncRNA-XIST induced the inhibition of the progression of glioma by way of triggering ROS production in a miR-137/SLC1A5 axis-dependent manner.

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Author contribution statement

ZXH conceived and designed research. SYF and LB conducted experiments and analyzed data. SYF wrote the manuscript. All authors read and approved the manuscript.

Author information

Correspondence to Xianhong Zhang.

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All aspects of the design and experimentation which related to live animals were in accordance with institutional guidelines of the Jining First People’s Hospital (China).

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The authors declare that they have no conflict of interest.

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Sun, Y., Lv, B. & Zhang, X. Knock-down of LncRNA-XIST induced glioma cell death and inhibited tumorigenesis by regulating miR-137/SLC1A5 axis-mediated ROS production. Naunyn-Schmiedeberg's Arch Pharmacol (2020). https://doi.org/10.1007/s00210-020-01831-3

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Keywords

  • Glioma
  • LncRNA-XIST
  • miR-137
  • SLC1A5
  • ROS