LUCAT1 promotes colorectal cancer tumorigenesis by targeting the ribosomal protein L40‐MDM2‐p53 pathway through binding with UBA52. Issue 4 (28th February 2019)

• Record Type: Journal Article
• Authors: Zhou, Qianwen; Hou, Zhibo; Zuo, Siyu; Zhou, Xin; Feng, Yadong; Sun, Yong; Yuan, Xiaoqin
• Is Part Of: Cancer science. Volume 110:Issue 4(2019)
• Page Start: 1194
• Page End: 1207
• Publication Date: 2019-02-28
• Subjects: colorectal cancer -- lung cancer associated transcript 1 -- MDM2 -- p53 -- UBA52; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13951
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : 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 RNAs (lncRNAs) 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 lncRNAs 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 lncRNA lung cancer‐associated transcript 1 ( LUCAT1 ) 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 LUCAT1 promoted CRC cell proliferation, apoptosis, migration, and invasion in vitro and in vivo. Furthermore, knockdown of LUCAT1 rendered CRC cells hypersensitive to oxaliplatin treatment. Mechanistically, bioinformatic analysis indicated that low expression of LUCAT1 was associated with the p53 signaling pathway. Chromatin isolation by RNA purification followed by mass spectrometry and RNA immunoprecipitation revealed that LUCAT1 bound with UBA52, which encodes ubiquitin and 60S ribosomal protein L40 (RPL40). We found that RPL40 functions in the ribosomal protein‐MDM2‐p53 pathway to regulate p53 expression. Taken together, our findings indicate that suppression of LUCAT1 induces CRC cell cycle arrest and apoptosis by binding UBA52 and activating the RPL40‐MDM2‐p53 pathway. These results implicate LUCAT1 as a potential prognostic biomarker and therapeutic target for CRC. Abstract : Our study found that lung cancer associated transcript 1 (LUCAT1) was significantly increased in colorectal cancer (CRC) tissues and suppression of LUCTA1 induced CRC cell cycle arrest and apoptosis via binding UBA52 and activating the RPL40‐MDM2‐p53 pathway. Our data indicated that LUCAT1 is involved in CRC progression and may serve as a potential prognostic biomarker and a therapeutic target for CRC.