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

Highlights: •Non-coding RNAs are found in the colonic crypt progenitor compartment. •Colonocytes transformed by ncNRFR are highly invasive and metastatic. •ncNRFR has a region similar to the miRNA, let-7 family. •ncNRFR expression alters let-7 activity as measured by reporter construct. •ncNRFR expression upregulates let-7b targets. -- Abstract: 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, andmore » its misregulation results in neoplastic transformation.« less
Authors:
 [1] ;  [2] ;  [2] ;  [3] ; ; ;  [4] ;  [5] ;  [6] ;  [1] ;  [2] ;  [1] ;  [2] ;  [2]
  1. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232 (United States)
  2. (United States)
  3. Department of Medicine, Vanderbilt University, Nashville, TN 37232 (United States)
  4. Department of Biomedical Informatics, Vanderbilt University, Nashville, TN 37232 (United States)
  5. Department of Pathology, Vanderbilt University, Nashville, TN 37232 (United States)
  6. Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232 (United States)
Publication Date:
OSTI Identifier:
22242130
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 440; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AGAR; HOMEOSTASIS; IN-SITU HYBRIDIZATION; LARGE INTESTINE; LET; METASTASES; MICE; NEOPLASMS; NUCLEAR REACTION ANALYSIS; POLYMERASE CHAIN REACTION; RNA