Identification of Key Pathways and Genes in the Orai2 Mediated Classical and Mesenchymal Subtype of Glioblastoma by Bioinformatic Analyses.

作者: Feng Yuan , Li Yi , Long Hai , Yingshuai Wang , Yihan Yang

DOI: 10.1155/2019/7049294

关键词:

摘要: Background. Ca2+ release-activated channels (CRAC) are the main entry pathway regulating intracellular concentration in a variety of cancer types. Orai2 is pore-forming subunit CRAC central neurons. To explore role glioblastoma (GBM), we investigated key pathways and genes Orai2-mediated GBM by bioinformatic analyses. Methods. Via The Cancer Genome Atlas (TCGA), French, Sun, Gene Expression Omnibus (GEO) (GDS3885) datasets, collected 1231 cases with RNA-seq data analyzed functional annotation gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analysis. Univariate multivariate survival analyses were applied to 823 patients data. Results. We discovered that was markedly upregulated compared normal brain samples lower-grade gliomas (LGG). Survival analysis found higher expression independently associated worse prognosis classical mesenchymal subtypes GBM. Simultaneously, tumors than other significantly correlated classical- mesenchymal-related genes. GO KEGG revealed involved JNK pathway. Through screening transcriptomic data, strong association between apoptosis, stemness, an epithelial-mesenchymal transition- (EMT-) like phenotype. Conclusion. As prognostic factor, obviously activated promotes glioma cell self-renewal, EMT-like These findings indicate could be candidate therapeutic target, especially for

参考文章(32)
Concetta Bubici, Salvatore Papa, JNK signalling in cancer: in need of new, smarter therapeutic targets British Journal of Pharmacology. ,vol. 171, pp. 24- 37 ,(2014) , 10.1111/BPH.12432
Hideaki Ueno, Arata Tomiyama, Hideki Yamaguchi, Takamasa Uekita, Takuya Shirakihara, Katsuhiko Nakashima, Naoki Otani, Kojiro Wada, Ryuichi Sakai, Hajime Arai, Kentaro Mori, Augmentation of invadopodia formation in temozolomide-resistant or adopted glioma is regulated by c-Jun terminal kinase–paxillin axis Biochemical and Biophysical Research Communications. ,vol. 468, pp. 240- 247 ,(2015) , 10.1016/J.BBRC.2015.10.122
Shizuka Seino, Hirohisa Kurachi, Keita Shibuya, Tsuyoshi Ohta, Manabu Seino, Chifumi Kitanaka, Shuhei Suzuki, Masashi Okada, Requirement of JNK signaling for self-renewal and tumor-initiating capacity of ovarian cancer stem cells. Anticancer Research. ,vol. 34, pp. 4723- 4731 ,(2014)
Ankit Kumar, Umesh K Singh, Suvarna G Kini, Vikas Garg, Saurabh Agrawal, Praveen K Tomar, Prateek Pathak, Anurag Chaudhary, Pratibha Gupta, Amrita Malik, JNK pathway signaling: a novel and smarter therapeutic targets for various biological diseases. Future Medicinal Chemistry. ,vol. 7, pp. 2065- 2086 ,(2015) , 10.4155/FMC.15.132
Murali Prakriya, Richard S. Lewis, Store-Operated Calcium Channels Physiological Reviews. ,vol. 95, pp. 1383- 1436 ,(2015) , 10.1152/PHYSREV.00020.2014
X. Hou, L. Pedi, M. M. Diver, S. B. Long, Crystal structure of the calcium release-activated calcium channel Orai. Science. ,vol. 338, pp. 1308- 1313 ,(2012) , 10.1126/SCIENCE.1228757
Kiranmai Alapati, Divya Kesanakurti, Jasti S. Rao, Venkata Ramesh Dasari, uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells. Stem Cell Research. ,vol. 12, pp. 716- 729 ,(2014) , 10.1016/J.SCR.2014.02.008
Ken-ichiro Matsuda, Atsushi Sato, Masashi Okada, Keita Shibuya, Shizuka Seino, Kaori Suzuki, Eriko Watanabe, Yoshitaka Narita, Soichiro Shibui, Takamasa Kayama, Chifumi Kitanaka, Targeting JNK for therapeutic depletion of stem-like glioblastoma cells Scientific Reports. ,vol. 2, pp. 516- 516 ,(2012) , 10.1038/SREP00516
MASASHI OKADA, KEITA SHIBUYA, ATSUSHI SATO, SHIZUKA SEINO, ERIKO WATANABE, SHUHEI SUZUKI, MANABU SEINO, CHIFUMI KITANAKA, Specific role of JNK in the maintenance of the tumor-initiating capacity of A549 human non-small cell lung cancer cells. Oncology Reports. ,vol. 30, pp. 1957- 1964 ,(2013) , 10.3892/OR.2013.2655
Rajender K. Motiani, María C. Hyzinski-García, Xuexin Zhang, Matthew M. Henkel, Iskandar F. Abdullaev, Yu-Hung Kuo, Khalid Matrougui, Alexander A. Mongin, Mohamed Trebak, STIM1 and Orai1 mediate CRAC channel activity and are essential for human glioblastoma invasion. Pflügers Archiv: European Journal of Physiology. ,vol. 465, pp. 1249- 1260 ,(2013) , 10.1007/S00424-013-1254-8