Open Access

The microRNA‑200 family acts as an oncogene in colorectal cancer by inhibiting the tumor suppressor RASSF2

  • Authors:
    • Jane V. Carter
    • Stephen J. O'brien
    • James F. Burton
    • Brent G. Oxford
    • Vince Stephen
    • Jake Hallion
    • Campbell Bishop
    • Norman J. Galbraith
    • Maurice R. Eichenberger
    • Harshini Sarojini
    • Eyas Hattab
    • Susan Galandiuk
  • View Affiliations

  • Published online on: August 16, 2019     https://doi.org/10.3892/ol.2019.10753
  • Pages: 3994-4007
  • Copyright: © Carter et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

This study aimed to determine whether manipulation of the microRNA‑200 (miR‑200) family could influence colon adenocarcinoma cell behavior. The miR‑200 family has a significant role in tumor suppression and functions as an oncogene. In vitro studies on gain and loss of function with small interfering RNA demonstrated that the miR‑200 family could regulate RASSF2 expression. Knockdown of the miR‑200 family in the HT‑29 colon cancer cell line increased KRAS expression but decreased signaling in the MAPK/ERK signaling pathway through reduced ERK phosphorylation. Increased expression of the miR‑200 family in the CCD‑841 colon epithelium cell line increased KRAS expression and led to increased signaling in the MAPK/ERK signaling pathway but increased ERK phosphorylation. Functionally, knockdown of the miR‑200 family led to decreased cell proliferation in the HT‑29 cells; therefore, increased miR‑200 family expression could increase cell proliferation in the CCD‑841 cell line. The present study included a large paired miR array dataset (n=632), in which the miR‑200 family was significantly found to be increased in colon cancer when compared with normal adjacent colon epithelium. In a miR‑seq dataset (n=199), the study found that miR‑200 family expression was increased in localized colon cancer compared with metastatic disease. Decreased expression was associated with poorer overall survival. The miR‑200 family directly targeted RASSF2 and was inversely correlated with RASSF2 expression (n=199, all P<0.001). Despite the well‑defined role of the miR‑200 family in tumor suppression, the present findings demonstrated a novel function of the miR‑200 family in tumor proliferation.

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October 2019
Volume 18 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Carter, J.V., O'brien, S.J., Burton, J.F., Oxford, B.G., Stephen, V., Hallion, J. ... Galandiuk, S. (2019). The microRNA‑200 family acts as an oncogene in colorectal cancer by inhibiting the tumor suppressor RASSF2. Oncology Letters, 18, 3994-4007. https://doi.org/10.3892/ol.2019.10753
MLA
Carter, J. V., O'brien, S. J., Burton, J. F., Oxford, B. G., Stephen, V., Hallion, J., Bishop, C., Galbraith, N. J., Eichenberger, M. R., Sarojini, H., Hattab, E., Galandiuk, S."The microRNA‑200 family acts as an oncogene in colorectal cancer by inhibiting the tumor suppressor RASSF2". Oncology Letters 18.4 (2019): 3994-4007.
Chicago
Carter, J. V., O'brien, S. J., Burton, J. F., Oxford, B. G., Stephen, V., Hallion, J., Bishop, C., Galbraith, N. J., Eichenberger, M. R., Sarojini, H., Hattab, E., Galandiuk, S."The microRNA‑200 family acts as an oncogene in colorectal cancer by inhibiting the tumor suppressor RASSF2". Oncology Letters 18, no. 4 (2019): 3994-4007. https://doi.org/10.3892/ol.2019.10753