%0 Journal Article
%T Establishment and characterization of CRISPR/Cas9©\mediated NF2
£¿/£¿ human mesothelial cell line: Molecular insight into fibroblast growth factor receptor 2 in malignant pleural mesothelioma
%A Akihito Inoko
%A Akinobu Ota
%A Hideki Murakami
%A Hiroyuki Konishi
%A Ichiro Hanamura
%A Md Lutfur Rahman
%A Md Wahiduzzaman
%A Shinobu Tsuzuki
%A Sivasundaram Karnan
%A Toshinori Hyodo
%A Yoshitaka Hosokawa
%J Archive of "Cancer Science".
%D 2019
%R 10.1111/cas.13871
%X Malignant pleural mesothelioma (MPM), a highly refractory tumor, is currently incurable due to the lack of an early diagnosis method and medication, both of which are urgently needed to improve the survival and/or quality of life of patients. NF2 is a tumor suppressor gene and is frequently mutated in MPM. Using a CRISPR/Cas9 system, we generated an NF2©\knockout human mesothelial cell line, MeT©\5A (NF2©\KO). In NF2©\KO cell clones, cell growth, clonogenic activity, migration activity, and invasion activity significantly increased compared with those in NF2©\WT cell clones. Complementary DNA microarray analysis clearly revealed the differences in global gene expression profile between NF2©\WT and NF2©\KO cell clones. Quantitative PCR analysis and western blot analysis showed that the upregulation of fibroblast growth factor receptor 2 (FGFR2) was concomitant with the increases in phosphorylation levels of JNK, c©\Jun, and retinoblastoma (Rb) in NF2©\KO cell clones. These increases were all abrogated by the exogenous expression of NF2 in the NF2©\KO clone. In addition, the disruption of FGFR2 in the NF2©\KO cell clone suppressed cell proliferation as well as the phosphorylation levels of JNK, c©\Jun, and Rb. Notably, FGFR2 was found to be highly expressed in NF2©\negative human mesothelioma tissues (11/12 cases, 91.7%) but less expressed in NF2©\positive tissues. Collectively, these findings suggest that NF2 deficiency might play a role in the tumorigenesis of human mesothelium through mediating FGFR2 expression; FGFR2 would be a candidate molecule to develop therapeutic and diagnostic strategies for targeting MPM with NF2 loss
%K CRISPR/Cas9
%K FGFR2
%K mesothelioma
%K microarray
%K NF2
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317947/