The long noncoding RNA TP73-AS1 promotes tumorigenicity of medulloblastoma cells

Mor Varon, Tal Levy, Gal Mazor, Hila Ben David, Ran Marciano, Yakov Krelin, Manu Prasad, Moshe Elkabets, David Pauck, Ulvi Ahmadov, Daniel Picard, Nan Qin, Arndt Borkhardt, Guido Reifenberger, Gabriel Leprivier, Marc Remke, Barak Rotblat

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Medulloblastoma is the most common malignant brain cancer in children. Since previous studies have mainly focused on alterations in the coding genome, our understanding of the contribution of long noncoding RNAs (lncRNAs) to medulloblastoma biology is just emerging. Using patient-derived data, we show that the promoter of lncRNA TP73-AS1 is hypomethylated and that the transcript is highly expressed in the SHH subgroup. Furthermore, high expression of TP73-AS1 is correlated with poor outcome in patients with TP53 wild-type SHH tumors. Silencing TP73-AS1 in medulloblastoma tumor cells induced apoptosis, while proliferation and migration were inhibited in culture. In vivo, silencing TP73-AS1 in medulloblastoma tumor cells resulted in reduced tumor growth, reduced proliferation of tumor cells, increased apoptosis and led to prolonged survival of tumor-bearing mice. Together, our study suggests that the lncRNA TP73-AS1 is a prognostic marker and therapeutic target in medulloblastoma tumors and serves as a proof of concept that lncRNAs are important factors in the disease.

Original languageEnglish
Pages (from-to)3402-3413
Number of pages12
JournalInternational Journal of Cancer
Volume145
Issue number12
DOIs
StatePublished - 15 Dec 2019

Keywords

  • gene regulation
  • oncogene
  • sonic hedgehog

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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