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

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. MiRNA-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 tumour 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.

MicroRNA‑744 suppresses cell proliferation and invasion of papillary thyroid cancer by directly targeting NOB1

“…miR-744 expression was downregulated in PTC tissues and cell lines. This observation is consistent with previous findings on the expression profile of miR-744 in colorectal cancer (17), cervical cancer (18) and hepatocellular carcinoma (19); however, miR-744 expression is upregulated in numerous types of human malignancy. For instance, miR-744 is overexpressed in the tissues, cell lines and plasma of pancreatic cancer (26,27).…”

“…miR-744 is also identified as a tumour suppressor in numerous types of human cancer. For example, miR-744 suppresses cell proliferation and invasion in colorectal cancer (17) and cervical cancer (18). miR-744 upregulation inhibits cell proliferation and promotes cell cycle arrest in hepatocellular carcinoma (31).…”

“…miR-744 is emerging as a cancer-associated miRNA in numerous types of human cancer, including colorectal cancer (17), cervical cancer (18) and hepatocellular carcinoma (19); however, the expression and specific functions of miR-744 in PTC are yet to be investigated, and the mechanism underlying the regulatory roles of miR-744 in PTC remains unknown. In the present study, we detected the expression of miR-744 in PTC tissues and cell lines, and examined the effects of miR-744 on the progression of PTC.…”

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“…The novel miR-663 targets are transforming growth factor-β1 [25], proteins PUMA/BBC3 and BTG2 [26], cyclin-dependent kinase inhibitor 2A [27]. The novel miR-744 targets are nuclear factor I X (NFIX) and heterogeneous nuclear ribonucleoprotein C (HNRNPC) [28], oncogene Notch1 [29], matrix metallopeptidase 9 (MMP-9) [30]. As these targets are also related to the cancer development, one cannot be absolutely sure that targeting eEF1A2 is the only mechanism of anti-cancer action of these microRNAs.…”

miR‐744‐5p inhibits cellular proliferation and invasion via targeting ARF1 in epithelial ovarian cancer

“…[12][13][14] Studies have indicated that miR-744-5p is lowly expressed in multiple cancers, like colorectal cancer, cervical cancer and glioblastoma, and overexpression of miR-744-5p can inhibit cell proliferation, migration, and invasion. [15][16][17] Moreover, miR-744-5p is also down-regulated in EOC cells, its upregulation could induce cell apoptosis. 12 However, the function of miR-744-5p in EOC cell proliferation and metastasis still remain largely unclear.…”