Identification of dysregulated lncRNAs profiling and metastasis‐associated lncRNAs in colorectal cancer by genome‐wide analysis

Abstract

The colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide, but the pathogenesis of CRC remains not well‐known. Increasing studies have highlighted the critical roles of long noncoding RNAs (lncRNAs) in tumorigenesis and cancer cells metastasis, however, the expression pattern, biological roles of lncRNAs, and the mechanisms responsible for their function in CRC remain elusive. In this study, we performed a genome‐wide comprehensive analysis of lncRNAs profiling and clinical relevance to identify novel lncRNAs for the further study in CRC. RNA sequencing and microarray data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were annotated and analyzed to find differentially expressed lncRNAs in CRC. Analysis of these datasets revealed that hundreds of lncRNAs expression are dysregulated in CRC tissues when compared with normal tissues. By genomic variation analyses, we identified that some of these lncRNAs dysregulation is associated with the copy number amplification or deletion. Moreover, many lncRNAs expression levels are significantly associated with CRC patients overall and recurrence‐free survivals, such as H19, LEF1‐AS1, and RP11‐296E3.2. Furthermore, we identified one liver metastasis‐associated lncRNA termed LUCAT1 in CRC by analyzing lncRNAs expression profiles in the CRC tissues from patients with liver metastasis compared with the CRC tissues without metastasis. Finally, loss‐of‐function assays determined that knockdown of LUCAT1 could impair CRC cells invasion. Taken together, aberrantly expressed lncRNAs may play critical roles in the development and liver metastasis of CRC, and our findings may provide useful resource for identification of novel biomarkers of CRC.

LUCAT1 promotes colorectal cancer tumorigenesis by targeting the ribosomal protein L40‐MDM2‐p53 pathway through binding with UBA52

“…Lung cancer‐associated transcript 1 is located on chromosome 5 and was first observed in the airway epithelium of smokers and in various cancer cell lines . In addition to lung cancer, LUCAT1 has also been reported to be involved in esophageal cancer, renal cell carcinoma, and cisplatin‐resistant ovarian cancer . Like other lncRNAs, LUCAT1 participates in carcinogenesis and cancer progression by regulating gene expression through chromatin modification, transcription, and post‐transcriptional procession.…”

“…LUCAT1 participates in methotrexate resistance regulation through the miR‐200c‐ABCB1 pathway . LUCAT1 has also been reported as a liver metastasis‐associated lncRNA through an analysis of CRC tissues from TCGA and Gene Expression Omnibus (GEO) databases; however, the underlying mechanisms are still unclear. Consistent with other studies, in which some lncRNAs including LUCAT1 are associated with chemotherapy resistance, our results revealed that LUCAT1 knockdown enhanced the apoptosis of CRC cells treated with oxaliplatin and 5‐FU.…”

A genome‐wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer

“…For example, Chen and colleagues performed a genome‐wide analysis of lncRNAs profiling and identified thousands of lncRNAs are differentially expressed in colorectal cancer 31. Moreover, a growing number of studies have demonstrated the function and underlying mechanisms of these dysregulated lncRNAs in cancer cells.…”

Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response

“…These findings suggest that LUCAT1 may act as a predictor for drug response in CRC patients and might be a useful biomarker for precise therapy in the clinic. Previous reports demonstrated that LUCAT1 is often upregulated in several types of cancer cells and promotes the proliferation, invasion or migration of these cells from many cancer types including CRC [23][24][25][26][27][28][29][30][31][32][33]. LUCAT1 can act as microRNA sponge [25,[29][30][31][32], or bind proteins, such as DNMT1, to regulate their stabilities or activities [23,24,26,28].…”