microRNA-320a inhibits tumor invasion by targeting neuropilin�1 and is associated with liver metastasis in colorectal cancer

Abstract

Abstract. MicroRNAs (miRNAs) have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that various miRNAs function as oncogenes or tumor suppressors in colorectal cancer (CRC), the role of miRNAs in mediating liver metastasis remains unexplored. The expression profile of miRNAs in liver metastasis and primary CRC tissues was analyzed by miRNA microarrays and verified by real-time polymerase chain reaction (PCR). In 62 CRC patients, the expression levels of miR-320a were determined by real-time PCR, and the effects on migration and invasion of miR-320a were determined using a transwell assay. miR-320a target genes were confirmed by luciferase assay, real-time PCR and Western blot analysis. A set of miRNAs was found to be dysregulated in the liver metastasis tissues compared to matched primary CRC tissues, and the expression levels of miR-320a were significantly decreased in the liver metastasis tissues examined. miR-320a was correlated with tumor progression in CRC. miR-320a was downregulated in liver metastatic colon cancer cells and inhibited liver metastatic colon cancer cell migration and invasion. miR-320a directly binds to the 3'UTR of neuropilin 1 (NRP-1), a protein that functions as a co-receptor of vascular epithelial growth factor. miR-320a downregulated the expression of NRP-1 at both the mRNA and protein levels. These data demonstrated that miR-320a may be useful for identifying CRC patients that are at an elevated risk for developing liver metastasis. Our findings suggest that miR-320a may be a novel therapeutic candidate for the treatment of colorectal cancer.

MicroRNA-149 Suppresses Colorectal Cancer Cell Migration and Invasion by Directly Targeting Forkhead Box Transcription Factor FOXM1

“…Wang' et al also found that serum microRNA-29a is a promising novel marker for early detection of colorectal liver metastasis [23]. The metastasis-inhibiting miRNAs (miR-342, 320a, 135a, miR-139, etc) in CRC are identified [24,25,26,27], while some metastasis-promoting miRNAs (miR-499-5p, miR-103/107, miR-155, etc) are also reported [28,29,30]. Has-miR-149, located on chromosome 2, has proven to be an essential miRNA implicated in the development and the progression of human malignancies.…”

Differential expression of microRNA-320a, -145, and -192 along the continuum of normal mucosa to high-grade dysplastic adenomas of the colorectum

“…This hypothesis is supported by findings that tumor metastasis is associated with a decrease and or loss of miR-320a expression. Zhang et al 17 reported loss of miR-320a expression in CRCs that metastasized to the liver, compared with their corresponding primary tumor. Arndt et al 18 showed that although a large proportion of metastatic CRC lesions retain the same epigenetic profile as their primary lesions, there is still enough variance between metastatic lesions and their corresponding primaries to suggest that perhaps downregulation of miR-320a may act late, after the lesion had metastasized.…”

Regulatory roles of microRNA-708 and microRNA-31 in proliferation, apoptosis and invasion of colorectal cancer cells

“…Colorectal cancer (CRC) is one of the most common malignant cancers and is the second leading cause of cancer-related mortality worldwide (1). The five-year survival rate of patients in the early stage is high, while that of late-stage patients is low due to metastasis.…”