Aberrantly Expressed LncRNAs(Long Noncoding RNAs) In Human Colon Cancer

Colon cancer is a significant cause of morbidity and mortality worldwide. More than 1 million individuals will develop colon cancer each year, and the disease-specific mortality rate is nearly 33% in the developed world. Initiation of colon cancer is a complex biological process, involving multiple genomic and epigenomic alterations. A better understanding of underlying mechanism that lead to tumorigenesis have contributed to identify molecular markers regarding etiology, prognosis, and even response to therapy for colon cancer.Long noncoding RNAs (lncRNAs) are defined as transcripts longer than 200 nucleotides (nt) with limited coding potential. LncRNAs can locate in nuclear or cytosolic fractions. They are usually transcribed by RNA polymerase Ⅱ but have no open reading frame. Moreover, lncRNAs display epigenetic features similar to protein-coding genes, such as trimethylation of histone 3 lysine 4 (H3K4me3) at the transcriptional start site (TSS) and trimethylation of histone 3 lysine 36 (H3K36me3) throughout the gene region. GENCODE v19 catalog report that human lncRNAs contains 13,870 lncRNA genes that produce 23,898 lncRNAs. LncRNAs function in a wide range of biological processes. Abnormalities (over-or under-expression, or genetic mutations) of lncRNAs have been shown to play critical roles in human disease pathogenesis including cancer formation and development. LncRNAs may function as oncogenes or tumor suppressors in the cancer and can regulate many key features of cancer, such as proliferation, apoptosis, autophagy and cancer metastasis. It has been reported that dysregulation of long noncoding RNAs plays important roles in cancer initiation and progression. Although many cancer-related lncRNAs have similar expression features as well as biologic function among tumors of different tissue origins, some lncRNAs have distinct expression pattern. It is urgently needed to discover the lncRNAs expression profile at the genomic level and find colon cancer-specific lncRNAs. This will be of great value to develop novel biomarkers for colon cancer diagnosis and therapy.In this study, we collected three paired colon cancer and non-tumor tissue. HE staining confirmed the histological types of cancer. Total RNA was isolated with Trizol reagent and purified by RNeasy kit. RNA quality was assessed using an Agilent Bioanalyzer. Labeled cDNAs were hybridized with Agilent Human lncRNA Microarray. Data were collected, and the initial analysis was performed using GeneSpring software. Hierarchical clustering showed systematic variations in the expression of lncRNAs and protein-coding RNAs between colon cancer and paired nontumor sample. Compared with adjacent non-tumor tissue, the expression level of 1461 mRNAs and 2137 lncRNAs were significantly upregulated while 916 mRNAs and 2178 lncRNAs were dramatically decreased, suggesting that lncRNAs expression profile was different between colon cancer and paired non-tumor tissue. GO (the Gene Ontology project) analysis and KEGG (the database of Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were used to study how to affect biological functions or pathways in these aberrantly expressed lncRNAs. Genome-wide lncRNA expression and co-expression with mRNA patterns were also analysed. Our results indicate that lncRNAs play important roles in many biological process of cancer, such as metabolism, angiogenesis, apoptosis, invasion and metastasis. Aberrantly expressed lncRNAs may regulate target genes through many transcription factors, including GABPA、MYC、ZEB1、MAX、TFAP2C、KAT2A、E2F4、SIN3A. QRT-PCR further conduct to validate the differential expression of two lncRNAs in 50 paired HCC and nontumor samples and confirmed the microarray data.In summary, we have identified nonoverlapping signatures of a number of lncRNAs and mRNAs that are up- or down-regulated in colon cancer, compared with paired peritumoral tissues. Bioinformatics analysis was conducted to find potential molecular mechanisms.