Oncotarget

Research Papers:

MicroRNA-761 promotes the sensitivity of colorectal cancer cells to 5-Fluorouracil through targeting FOXM1

Shuguang Cao, Limiao Lin, Xuanping Xia and Hao Wu _

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Oncotarget. 2018; 9:321-331. https://doi.org/10.18632/oncotarget.20109

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Abstract

Shuguang Cao1, Limiao Lin1, Xuanping Xia1 and Hao Wu1

1Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China

Correspondence to:

Hao Wu, email: [email protected]

Keywords: colorectal cancer, miR-761, 5-Fluorouracil, FOXM1

Received: June 06, 2017     Accepted: July 25, 2017     Published: August 10, 2017

ABSTRACT

Resistance to chemotherapy is a big challenge for treatment of patients with colorectal cancer; however; the mechanism underlying chemoresistance in colorectal cancer cell has not been elucidated. MicroRNAs (miRNAs) are new players in the development of drug chemoresistance. In our study, we indicated that overexpression of miR-761 promoted the sensitivity of colorectal cancer cells to 5-Fluorouracil (5-FU). miR-761 expression was downregulated in colorectal cancer cell lines and tissues. miR-761 expression was lower in patients with low grade than in patients with high grade. In additon, we showed that elevated expression of miR-761 suppressed colorectal cancer cell proliferation, cell cycle, colony formation and cell invasion. We identified that FOXM1 was a direct target gene of miR-761 in colorectal cancer cell. FOXM1 expression was upregulated in colorectal cancer tissues compare to the adjacent non-tumor tissues. MiR-761 expression was negatively associated with the expression of FOXM1 in colorectal cancer tissues. Elevated expression of FOXM1 suppressed the sensitivity of miR-761-overexpressing HT29 cells to 5-FU. We also indicated that FOXM1 overexpression promoted cell proliferation, cycle and invasion of miR-761-overexpressing HT29 cells. These data suggested that miR-761 played a tumor suppressor miRNA in colorectal cancer progression and reduced miR-761 expression might be a major mechanism for 5-FU resistance in colorectal cancer cell.


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