Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, MN, USA.
RNA Biol. 2011 May-Jun;8(3):496-505. doi: 10.4161/rna.8.3.14800. Epub 2011 May 1.
More than 98% of the human genome is comprised of non-protein coding sequences. Interestingly, a considerable fraction of these sequences is transcribed into non-protein coding RNA transcripts. These transcripts range in size from very small RNAs such as the miRNAs (20-25 base pairs) to transcripts that can range up to 100 kb or more. Some longer non-coding RNAs (lncRNAs) have been found to play important regulatory roles within cells. In this report, we demonstrate that LSINCT5 is a 2.6 Kb polyadenylated, long stress-induced non-coding transcript that is on the negative strand, localized in the nucleus and potentially transcribed by RNA polymerase III. LSINCT5 is overexpressed in breast and ovarian cancer cell lines and tumor tissues, relative to their normal counterpart. In addition, knocking down the expression of LSINCT5 in cancer-derived cell lines causes a decrease in cellular proliferation. Finally, we identified 95 genes with more than 2-fold changes when knocking down LSINCT5 expression by using the Affymetrix U133 Plus 2 array. We chose a subset of these genes to validate using qPCR and found that ten of these genes were indeed significantly affected by the LSINCT5 knockdown. Interestingly, two genes that were significantly downregulated were the lncRNA NEAT-1 and a protein coding gene PSPC1. We have therefore characterized a novel lncRNA that is overexpressed in breast and ovarian cancers, enhances cellular proliferation and may play a significant role in multiple processes.
人类基因组中超过 98%由非蛋白编码序列组成。有趣的是，这些序列的相当一部分被转录为非蛋白编码 RNA 转录本。这些转录本的大小范围从非常小的 RNA（如 miRNA[20-25 个碱基对]）到可长达 100 kb 或更长的转录本。一些较长的非编码 RNA（lncRNA）已被发现在细胞内发挥重要的调节作用。在本报告中，我们证明 LSINCT5 是一种 2.6 kb 的多聚腺苷酸化的长应激诱导非编码转录本，位于负链上，定位于细胞核内，可能由 RNA 聚合酶 III 转录。LSINCT5 在乳腺癌和卵巢癌细胞系和肿瘤组织中过表达，相对于其正常对应物。此外，在癌症衍生的细胞系中敲低 LSINCT5 的表达会导致细胞增殖减少。最后，我们通过使用 Affymetrix U133 Plus 2 阵列确定了 95 个基因的表达变化超过 2 倍，当敲低 LSINCT5 表达时。我们选择了其中一部分基因进行 qPCR 验证，发现其中 10 个基因确实受到 LSINCT5 敲低的显著影响。有趣的是，两个显著下调的基因是 lncRNA NEAT-1 和一个蛋白编码基因 PSPC1。因此，我们已经描述了一种在乳腺癌和卵巢癌中过表达的新型 lncRNA，它增强了细胞增殖，并可能在多个过程中发挥重要作用。
