Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, United States; Department of Medicine, Vanderbilt University, Nashville, TN 37232, United States; Department of Veterans Affairs Medical Center, Nashville, TN 37232, United States.
Biochem Biophys Res Commun. 2013 Oct 11;440(1):99-104. doi: 10.1016/j.bbrc.2013.09.040. Epub 2013 Sep 14.
Recent progress has been made in the identification of protein-coding genes and miRNAs that are expressed in and alter the behavior of colonic epithelia. However, the role of long non-coding RNAs (lncRNAs) in colonic homeostasis is just beginning to be explored. By gene expression profiling of post-mitotic, differentiated tops and proliferative, progenitor-compartment bottoms of microdissected adult mouse colonic crypts, we identified several lncRNAs more highly expressed in crypt bottoms. One identified lncRNA, designated non-coding Nras functional RNA (ncNRFR), resides within the Nras locus but appears to be independent of the Nras coding transcript. Stable overexpression of ncNRFR in non-transformed, conditionally immortalized mouse colonocytes results in malignant transformation, as determined by growth in soft agar and formation of highly invasive tumors in nude mice. Moreover, ncNRFR appears to inhibit the function of the tumor suppressor let-7. These results suggest precise regulation of ncNRFR is necessary for proper cell growth in the colonic crypt, and its misregulation results in neoplastic transformation.
最近在鉴定蛋白质编码基因和 miRNA 方面取得了进展，这些基因和 miRNA 在结肠上皮细胞中表达并改变其行为。然而，长非编码 RNA（lncRNA）在结肠稳态中的作用才刚刚开始被探索。通过对微切割的成年小鼠结肠隐窝有丝分裂后分化的顶部和增殖的祖细胞底部进行基因表达谱分析，我们鉴定了一些在隐窝底部表达更高的 lncRNA。一个被鉴定的 lncRNA，命名为非编码 Nras 功能 RNA（ncNRFR），位于 Nras 基因座内，但似乎与 Nras 编码转录本无关。稳定过表达 ncNRFR 在非转化、条件永生化的小鼠结肠细胞中导致恶性转化，这可通过软琼脂中的生长和裸鼠中形成高度侵袭性肿瘤来确定。此外，ncNRFR 似乎抑制了肿瘤抑制因子 let-7 的功能。这些结果表明，ncNRFR 的精确调节对于结肠隐窝中细胞的正常生长是必要的，其失调导致肿瘤转化。
