miR-23a promotes the transition from indolent to invasive colorectal cancer

Sohail Jahid, Jian Sun, Robert A. Edwards, Diana Dizon, Nicole C. Panarelli, Jeffrey W. Milsom, Shaheen S. Sikandar, Zeynep H. Gümüş, Steven M. Lipkin

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Colorectal cancer is a classic example of a tumor that progresses through multiple distinct stages in its evolution. To understand the mechanisms regulating the transition from indolent to invasive disease, we profiled somatic copy number alterations in noninvasive adenomas and invasive adenocarcinomas from Apc and DNA mismatch repair (MMR) mutant mouse models. We identified a recurrent amplicon on mouse chromosome 8 that encodes microRNA (miRNA) 23a and -27a (miR). miR-23a and -27a levels are upregulated in mouse intestinal adenocarcinomas, primary tumors from patients with stage I/II colorectal cancers, as well as in human colorectal cancer cell lines and cancer stem cells. Functionally, miR-23a promotes the migration and invasion of colorectal cancer cells and stem cells, whereas miR-27a primarily promotes proliferation. We computationally and experimentally validated that metastasis suppressor 1 (MTSS1) is a direct miR-23a target and similarly validated that the ubiquitin ligase FBXW7 is a direct miR-27a target. Analyses of computationally predicted target genes in microarray data sets of patients with colorectal cancers are consistent with a role for miR-23a, but not miR-27a, specifically in invasive colorectal cancers. SIGNIFICANCE: Understanding the mechanisms regulating the transition from indolent adenomas to invasive and metastatic colorectal cancers is critical to improving patient outcomes. Our study highlights roles of miR-23a and miR-27a in tumor progression and supports a potential mechanistic role for miR-23a in the transition from indolent to invasive colorectal cancers.

Original languageEnglish (US)
Pages (from-to)540-553
Number of pages14
JournalCancer Discovery
Volume2
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

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Colorectal Neoplasms
Adenoma
Adenocarcinoma
Chromosomes, Human, Pair 8
Neoplasms
DNA Mismatch Repair
Neoplastic Stem Cells
Ligases
Ubiquitin
MicroRNAs
Stem Cells
Neoplasm Metastasis
Cell Line
Genes

ASJC Scopus subject areas

  • Oncology

Cite this

Jahid, S., Sun, J., Edwards, R. A., Dizon, D., Panarelli, N. C., Milsom, J. W., ... Lipkin, S. M. (2012). miR-23a promotes the transition from indolent to invasive colorectal cancer. Cancer Discovery, 2(6), 540-553. https://doi.org/10.1158/2159-8290.CD-11-0267

miR-23a promotes the transition from indolent to invasive colorectal cancer. / Jahid, Sohail; Sun, Jian; Edwards, Robert A.; Dizon, Diana; Panarelli, Nicole C.; Milsom, Jeffrey W.; Sikandar, Shaheen S.; Gümüş, Zeynep H.; Lipkin, Steven M.

In: Cancer Discovery, Vol. 2, No. 6, 06.2012, p. 540-553.

Research output: Contribution to journalArticle

Jahid, S, Sun, J, Edwards, RA, Dizon, D, Panarelli, NC, Milsom, JW, Sikandar, SS, Gümüş, ZH & Lipkin, SM 2012, 'miR-23a promotes the transition from indolent to invasive colorectal cancer', Cancer Discovery, vol. 2, no. 6, pp. 540-553. https://doi.org/10.1158/2159-8290.CD-11-0267
Jahid, Sohail ; Sun, Jian ; Edwards, Robert A. ; Dizon, Diana ; Panarelli, Nicole C. ; Milsom, Jeffrey W. ; Sikandar, Shaheen S. ; Gümüş, Zeynep H. ; Lipkin, Steven M. / miR-23a promotes the transition from indolent to invasive colorectal cancer. In: Cancer Discovery. 2012 ; Vol. 2, No. 6. pp. 540-553.
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