Long, abundantly expressed non-coding transcripts are altered in cancer

Abstract

Recent studies with tiling arrays have revealed more genomic transcription than previously anticipated. Whole new groups of non-coding transcripts (NCTs) have been detected. Some of these NCTs, including miRNAs, can regulate gene expression. To date, most known NCTs studied have been relatively short, but several important regulatory NCTs, including XIST, MALAT-1, BC1 and BC200, are considerably larger in length and represent a novel class of long, non-coding RNA species. Whole-genome tiling arrays were utilized to identify novel long NCTs across the entire human genome. Our results have identified a new group of long (>400 nt), abundantly expressed NCTs and have found that a subset of these are also highly evolutionarily conserved. In this report, we have begun to characterize 15 long, conserved NCTs. Quantitative real-time RT-PCR was used to analyze their expression in different normal human tissue and also in breast and ovarian cancers. We found altered expression of many of these NCTs in both cancer types. In addition, several of these NCTs have consistent mutations when sequences of normal samples were compared with a panel of cancer-derived cell lines. One NCT was found to be consistently mutated in a panel of endometrial cancers compared with matched normal blood. These NCTs were among the most abundantly expressed transcripts detected. There are probably many long, conserved NCTs, albeit with lower levels of expression. Although the function of these NCTs is currently unknown, our study indicates that they may play an important function in both normal cells and in cancer development.

Two Novel Splice Variants of SOX2OT, SOX2OT-S1, and SOX2OT-S2 are Coupregulated with SOX2 and OCT4 in Esophageal Squamous Cell Carcinoma

“…Recent reports of misregulated expression of lncRNAs across many cancer types suggest that their aberrant expression might be a major cause of tumorigenesis, and those different types of cancers can be distinguished according to their altered lncRNAs expression signatures [7][8][9]. LncRNAs are also introduced as a newly emerging class of oncogene and tumor-suppressor genes [10].…”

Differential expression of long non-coding RNAs in bleomycin-induced lung fibrosis

“…They play an important role in imprinting (7), enhancing various biological functions (8), X chromosome inactivation (9), chromatin structure (10) and genomic rearrangement during the generation of antibody diversity (11). Thus, lncRNAs are critical for normal development and, in many cases, are deregulated in diseases, such as cancer (12).…”

Long non-coding RNAs in cancer

“…Cellular MALAT1 can be posttranscriptionally processed to yield the short, highly conserved, tRNA-like molecule mascRNA and the long MALAT1 transcript, which contains a poly(A) tail-like moiety [57]. MALAT1 is expressed in normal human tissues and exhibits increased expression in cancers of the breast, prostate, colon, liver, lung and others [58]. The expression level of MALAT1 in the metastatic tumors of non-small cell lung cancer (NSCLC) patients is three times higher than that of patients lacking metastatic tumors, and patients harboring tumors with elevated MALAT1 expression have a poor prognosis [59].…”