MicroRNA-744 Inhibits Cellular Proliferation and Invasion of Colorectal Cancer by Directly Targeting Oncogene Notch1

MicroRNA-744通过直接靶向致癌基因Notch1抑制结直肠癌细胞增殖和侵袭

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Abstract

Accumulated studies have strongly implicated aberrantly expressed microRNAs (miRNAs) in carcinogenesis and cancer progression of various cancers, including colorectal cancer (CRC). Hence, a comprehensive study of miRNAs and their association with CRC may be a promising therapeutic method for patients with this malignancy. MicroRNA-744 (miR-744) is abnormally expressed in several types of human cancer. Thus far, little is known about the expression, biological roles, and exact mechanisms of miR-744 in CRC. Thus, the present study measured the expression level of miR-744 and investigated its roles and associated molecular mechanisms in CRC. This study demonstrated that miR-744 expression was significantly underexpressed in CRC tissues and cell lines. Low miR-744 expression was positively associated with lymphatic metastasis and TNM stage. Functional experiments revealed that miR-744 overexpression obviously inhibited the proliferation and invasion of CRC cells. Furthermore, Notch1 was identified as a direct target of miR-744 in CRC. Moreover, the inhibition of Notch1 phenocopied the inhibitory effects of miR-744 overexpression on CRC cells. Restored Notch1 expression markedly rescued the tumor-suppressive effects of miR-744 overexpression on CRC cells. Overall, miR-744 exhibits an essential role in CRC progression, and the miR-744/Notch1 axis may provide novel insights into future treatments for patients with CRC.

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