The long noncoding RNA TP73‐AS1 promotes tumorigenicity of medulloblastoma cells. Issue 12 (12th June 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: International journal of cancer. Volume 145:Issue 12(2019)
• Page Start: 3402
• Page End: 3413
• Publication Date: 2019-06-12
• Subjects: gene regulation -- sonic hedgehog -- oncogene; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32400
• Languages: English
• ISSNs: 0020-7136

Abstract

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. Abstract : What's new? Long non‐coding RNAs (lncRNAs) influence diverse cellular activities, including gene expression and the activity of adjacent genes. Hence, some lncRNAs are implicated in cancer. Here, the lncRNA TP73‐AS1 was investigated for a possible functional role in medulloblastoma. TP73‐AS1 was found to be overexpressed in medulloblastoma cells, with expression levels correlated to TP73‐AS1 hypomethylation. Functionally, TP73‐AS1 prevented cell death and promoted proliferation and tumorigenicity of medulloblastoma tumor cells in vitro and in vivo . Mice injected with TP73‐AS1‐ knockdown medulloblastoma tumor cells exhibited reduced tumor growth and improved survival. The findings identify TP73‐AS1 as a potential marker and therapeutic target in medulloblastoma.