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

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 interferin...

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Veröffentlicht in:Oncology letters 2019-10, Vol.18 (4), p.3994-4007
Hauptverfasser: Carter, Jane V, O'brien, Stephen J, Burton, James F, Oxford, Brent G, Stephen, Vince, Hallion, Jake, Bishop, Campbell, Galbraith, Norman J, Eichenberger, Maurice R, Sarojini, Harshini, Hattab, Eyas, Galandiuk, Susan
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Sprache:eng
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Zusammenfassung: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
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2019.10753