Frontiers in Oncology (Aug 2021)

Small RNA Sequencing Identifies PIWI-Interacting RNAs Deregulated in Glioblastoma—piR-9491 and piR-12488 Reduce Tumor Cell Colonies In Vitro

  • Michael Bartos,
  • Frantisek Siegl,
  • Alena Kopkova,
  • Lenka Radova,
  • Jan Oppelt,
  • Marek Vecera,
  • Tomas Kazda,
  • Radim Jancalek,
  • Michal Hendrych,
  • Marketa Hermanova,
  • Petra Kasparova,
  • Zuzana Pleskacova,
  • Vaclav Vybihal,
  • Pavel Fadrus,
  • Martin Smrcka,
  • Radek Lakomy,
  • Radim Lipina,
  • Tomas Cesak,
  • Ondrej Slaby,
  • Ondrej Slaby,
  • Ondrej Slaby,
  • Jiri Sana,
  • Jiri Sana,
  • Jiri Sana

DOI
https://doi.org/10.3389/fonc.2021.707017
Journal volume & issue
Vol. 11

Abstract

Read online

Glioblastoma (GBM) is the most frequently occurring primary malignant brain tumor of astrocytic origin. To change poor prognosis, it is necessary to deeply understand the molecular mechanisms of gliomagenesis and identify new potential biomarkers and therapeutic targets. PIWI-interacting RNAs (piRNAs) help in maintaining genome stability, and their deregulation has already been observed in many tumors. Recent studies suggest that these molecules could also play an important role in the glioma biology. To determine GBM-associated piRNAs, we performed small RNA sequencing analysis in the discovery set of 19 GBM and 11 non-tumor brain samples followed by TaqMan qRT-PCR analyses in the independent set of 77 GBM and 23 non-tumor patients. Obtained data were subsequently bioinformatically analyzed. Small RNA sequencing revealed 58 significantly deregulated piRNA molecules in GBM samples in comparison with non-tumor brain tissues. Deregulation of piR-1849, piR-9491, piR-12487, and piR-12488 was successfully confirmed in the independent groups of patients and controls (all p < 0.0001), and piR-9491 and piR-12488 reduced GBM cells’ ability to form colonies in vitro. In addition, piR-23231 was significantly associated with the overall survival of the GBM patients treated with Stupp regimen (p = 0.007). Our results suggest that piRNAs could be a novel promising diagnostic and prognostic biomarker in GBM potentially playing important roles in gliomagenesis.

Keywords