PTENP1-AS contributes to BRAF inhibitor resistance and is associated with adverse clinical outcome in stage III melanoma.
作者： Dan Grandér , Sakari Kauppinen , Katja Pokrovskaja Tamm , Per Johnsson , Rainer Tuominen
DOI: 10.1038/S41598-021-89389-9
关键词: EZH2 、 Transcription (biology) 、 Antisense RNA 、 Melanoma 、 Mutation 、 Cancer research 、 Stage III melanoma 、 PTEN 、 Drug resistance 、 Medicine
摘要: BRAF inhibitors (BRAFi) selectively target oncogenic BRAFV600E/K and are effective in 80% of advanced cutaneous malignant melanoma cases carrying the V600 mutation. However, development drug resistance limits their clinical efficacy. Better characterization underlying molecular processes is needed to further improve treatments. We previously demonstrated that transcription PTEN negatively regulated by pseudogene antisense RNA, PTENP1-AS, here we investigated impact this transcript on outcome BRAFi melanoma. observed increased expression levels PTENP1-AS resistant cells associated with enrichment EZH2 H3K27me3 at promoter, consequently reducing PTEN. Further, showed targeting sensitized treatment high stage III correlated poor survival. Collectively, data presented show a promising for re-sensitizing also possible prognostic marker
nature.com 
sci-hub.st 参考文章(22)
Per Johnsson, Kevin V. Morris, Dan Grandér, Pseudogenes: a novel source of trans-acting antisense RNAs. Methods of Molecular Biology. ,vol. 1167, pp. 213- 226 ,(2014) , 10.1007/978-1-4939-0835-6_14
Laura Poliseno, Leonardo Salmena, Jiangwen Zhang, Brett Carver, William J. Haveman, Pier Paolo Pandolfi, A coding-independent function of gene and pseudogene mRNAs regulates tumour biology Nature. ,vol. 465, pp. 1033- 1038 ,(2010) , 10.1038/NATURE09144
David Dankort, David P Curley, Robert A Cartlidge, Betsy Nelson, Anthony N Karnezis, William E Damsky Jr, Mingjian J You, Ronald A DePinho, Martin McMahon, Marcus Bosenberg, BrafV600E cooperates with Pten loss to induce metastatic melanoma Nature Genetics. ,vol. 41, pp. 544- 552 ,(2009) , 10.1038/NG.356
Baikang Pei, Cristina Sisu, Adam Frankish, Cédric Howald, Lukas Habegger, Xinmeng Mu, Rachel Harte, Suganthi Balasubramanian, Andrea Tanzer, Mark Diekhans, Alexandre Reymond, Tim J Hubbard, Jennifer Harrow, Mark B Gerstein, The GENCODE pseudogene resource Genome Biology. ,vol. 13, pp. 1- 26 ,(2012) , 10.1186/GB-2012-13-9-R51
Dingxie Liu, Xuan Liu, Mingzhao Xing, Activities of multiple cancer-related pathways are associated with braf mutation and predict the resistance to braf/mek inhibitors in melanoma cells Cell Cycle. ,vol. 13, pp. 208- 219 ,(2014) , 10.4161/CC.26971
Peter G. Hawkins, Kevin V. Morris, Transcriptional regulation of Oct4 by a long non-coding RNA antisense to Oct4-pseudogene 5. Transcription. ,vol. 1, pp. 165- 175 ,(2010) , 10.4161/TRNS.1.3.13332
A. Cecilia Munko, Elizabeth Wood, Inna V. Fedorenko, Vernon K. Sondak, Alexander R.A. Anderson, Antoni Ribas, Maurizia Dalla Palma, Katherine L. Nathanson, John M. Koomen, Jane L. Messina, Keiran S.M. Smalley, Kim H.T. Paraiso, Yun Xiang, Vito W. Rebecca, Ethan V. Abel, Y. Ann Chen, PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression Cancer Research. ,vol. 71, pp. 2750- 2760 ,(2011) , 10.1158/0008-5472.CAN-10-2954
Emmanuelle Viré, Carmen Brenner, Rachel Deplus, Loïc Blanchon, Mario Fraga, Céline Didelot, Lluis Morey, Aleyde Van Eynde, David Bernard, Jean-Marie Vanderwinden, Mathieu Bollen, Manel Esteller, Luciano Di Croce, Yvan De Launoit, François Fuks, None, The Polycomb group protein EZH2 directly controls DNA methylation Nature. ,vol. 439, pp. 871- 874 ,(2006) , 10.1038/NATURE04431
Florian A. Karreth, Yvonne Tay, Daniele Perna, Ugo Ala, Shen Mynn Tan, Alistair G. Rust, Gina DeNicola, Kaitlyn A. Webster, Dror Weiss, Pedro A. Perez-Mancera, Michael Krauthammer, Ruth Halaban, Paolo Provero, David J. Adams, David A. Tuveson, Pier Paolo Pandolfi, In Vivo Identification of Tumor- Suppressive PTEN ceRNAs in an Oncogenic BRAF-Induced Mouse Model of Melanoma Cell. ,vol. 147, pp. 382- 395 ,(2011) , 10.1016/J.CELL.2011.09.032
Johan Falkenius, Joakim Lundeberg, Hemming Johansson, Rainer Tuominen, Marianne Frostvik-Stolt, Johan Hansson, Suzanne Egyhazi Brage, High expression of glycolytic and pigment proteins is associated with worse clinical outcome in stage III melanoma. Melanoma Research. ,vol. 23, pp. 452- 460 ,(2013) , 10.1097/CMR.0000000000000027