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The long noncoding RNA TP73‐AS1 promotes tumorigenicity of medulloblastoma cells
Author(s) -
Varon Mor,
Levy Tal,
Mazor Gal,
Ben David Hila,
Marciano Ran,
Krelin Yakov,
Prasad Manu,
Elkabets Moshe,
Pauck David,
Ahmadov Ulvi,
Picard Daniel,
Qin Nan,
Borkhardt Arndt,
Reifenberger Guido,
Leprivier Gabriel,
Remke Marc,
Rotblat Barak
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32400
Subject(s) - medulloblastoma , gene silencing , long non coding rna , cancer research , biology , antisense rna , apoptosis , rna , gene , genetics
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.