Open AccessLUCAT1 promotes colorectal cancer tumorigenesis by targeting the ribosomal protein L40‐ MDM 2‐p53 pathway through binding with UBA 52
Author(s) -
Zhou Qianwen,
Hou Zhibo,
Zuo Siyu,
Zhou Xin,
Feng Yadong,
Sun Yong,
Yuan Xiaoqin
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13951
Subject(s) - carcinogenesis , biology , gene knockdown , rna , cancer research , transcriptome , rna binding protein , long non coding rna , colorectal cancer , microbiology and biotechnology , cancer , ribosomal protein , chromatin immunoprecipitation , downregulation and upregulation , ribosome , apoptosis , gene expression , gene , genetics , promoter
Colorectal cancer ( CRC ) is the third most commonly diagnosed cancer in both men and women in the USA. However, the underlying molecular mechanisms that drive CRC tumorigenesis are still not clear. Several studies have reported that long noncoding RNA s (lnc RNA s) have important roles in tumor development. Here, we undertook a transcriptome microarray analysis in 6 pairs of CRC tissues and their corresponding adjacent normal tissues. A total of 1705 differentially expressed lnc RNA s were detected in CRC tissues at stages I/ II and III / IV (fold change greater than or equal to 2 or less than or equal to 0.5). Among them, we found that the lnc RNA lung cancer‐associated transcript 1 ( LUCAT 1 ) was upregulated in CRC tissues and was closely associated with poor overall survival of CRC patients, through analysis of clinical data and The Cancer Genome Atlas. Functional studies indicated that LUCAT 1 promoted CRC cell proliferation, apoptosis, migration, and invasion in vitro and in vivo. Furthermore, knockdown of LUCAT 1 rendered CRC cells hypersensitive to oxaliplatin treatment. Mechanistically, bioinformatic analysis indicated that low expression of LUCAT 1 was associated with the p53 signaling pathway. Chromatin isolation by RNA purification followed by mass spectrometry and RNA immunoprecipitation revealed that LUCAT 1 bound with UBA 52 , which encodes ubiquitin and 60S ribosomal protein L40 ( RPL 40). We found that RPL 40 functions in the ribosomal protein‐ MDM 2‐p53 pathway to regulate p53 expression. Taken together, our findings indicate that suppression of LUCAT 1 induces CRC cell cycle arrest and apoptosis by binding UBA 52 and activating the RPL 40‐ MDM 2‐p53 pathway. These results implicate LUCAT 1 as a potential prognostic biomarker and therapeutic target for CRC .