RRC ID 72181
著者 Tanaka Y, Kambayashi H, Yamamoto A, Onishi I, Sugita K, Matsumura M, Ishibashi S, Ikeda M, Yamamoto K, Kitagawa M, Kurata M.
タイトル Efficient Identification of the MYC Regulator with the Use of the CRISPR Library and Context-Matched Database Screenings.
ジャーナル Int J Mol Sci
Abstract MYC is a major oncogene that plays an important role in cell proliferation in human cancers. Therefore, the mechanism behind MYC regulation is a viable therapeutic target for the treatment of cancer. Comprehensive and efficient screening of MYC regulators is needed, and we had previously established a promoter screening system using fluorescent proteins and the CRISPR library. For the efficient identification of candidate genes, a database was used, for which mRNA expression was correlated with MYC using datasets featuring "Similar" and "Not exactly similar" contexts. INTS14 and ERI2 were identified using datasets featuring the "Similar" context group, and INTS14 and ERI2 were capable of enhancing MYC promoter activity. In further database analysis of human cancers, a higher expression of MYC mRNA was observed in the INTS14 mRNA high-expressing prostate and liver cancers. The knockdown of INTS14 in prostate cell lines resulted in decreased MYC mRNA and protein expression and also induced G0/1 arrest. This study confirmed that CRISPR screening combined with context-matched database screening is effective in identifying genes that regulate the MYC promoter. This method can be applied to other genes and is expected to be useful in identifying the regulators of other proto-oncogenes.
巻・号 23(14)
公開日 2022-7-13
DOI 10.3390/ijms23147723
PII ijms23147723
PMID 35887071
PMC PMC9317319
MeSH Cell Line, Tumor Clustered Regularly Interspaced Short Palindromic Repeats* Gene Expression Regulation, Neoplastic Humans Liver Neoplasms* / genetics Male Proto-Oncogene Proteins c-myc / genetics Proto-Oncogene Proteins c-myc / metabolism Proto-Oncogenes RNA, Messenger / genetics
IF 4.556
リソース情報
ヒト・動物細胞 PC-3(RCB2145)