Malignant transformation of colonic epithelial cells by a colon-derived long noncoding RNA.

Franklin JL, Rankin CR, Levy S, Snoddy JR, Zhang B, Washington MK, Thomson JM, Whitehead RH, Coffey RJ
Biochem Biophys Res Commun. 2013 440 (1): 99-104

PMID: 24045012 · PMCID: PMC3875348 · DOI:10.1016/j.bbrc.2013.09.040

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

MeSH Terms (11)

Animals Cell Transformation, Neoplastic Colon Colonic Neoplasms Epithelial Cells Gene Expression Profiling Gene Expression Regulation, Neoplastic Mice Mice, Nude MicroRNAs RNA, Long Noncoding

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