The long noncoding RNA LUCAT1 promotes CRC tumorigenesis by targeting RPL40‐MDM2‐p53 pathway through binding with UBA52

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women in the United States. However, the underlying molecular mechanisms that drive CRC tumorigenesis are still not clear. Several studies have demonstrated that long non‐coding RNAs (lncRNAs) have important roles in tumor development. Here, we performed a transcriptome microarray analysis in six pairs of CRC tissues and their corresponding adjacent normal tissues. A total of 1,705 differentially expressed lncRNAs were detected in CRC tissues at stages I/II and III/IV (fold change ≥ 2 or ≤ 0.5). Among them, we found that the lncRNA LUCAT1 was upregulated in CRC tissues and was closely associated with poor overall survival of CRC patients, through analysis of clinical and TCGA data. Functional studies demonstrated 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 via binding UBA52 and activating the RPL40–MDM2–p53 pathway. These results implicate LUCAT1 as a potential prognostic biomarker and therapeutic target for CRC.

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