Abstract
Protein tyrosine phosphatase 1B (PTP1B) has been reported as an oncogene in hepatocellular carcinoma (HCC). However, how PTP1B is regulated in HCC remains unclear. MicroRNAs (miRNAs) are a class of small non-coding RNAs involved many biological processes including tumorigenesis. In this study, we investigated whether miRNA participated in the regulation of PTP1B in HCC. We found that miR-206, which was down-regulated during tumorigenesis, inhibited HCC cell proliferation and invasion. Overexpression of miR-206 inhibited proliferation, invasion, and migration of HCC cell lines HepG2 and Huh7. Mechanistically, we demonstrated that miR-206 directly targeted PTP1B by binding to the 3′-UTR of PTP1B mRNA as demonstrated by the luciferase reporter assay. Overexpression miR-206 inhibited PTP1B expression while miR-206 inhibition enhanced PTP1B expression in HepG2 and Huh7 cells. Functionally, the regulatory effect on cell proliferation/migration/invasion of miR-206 was reversed by PTP1B overexpression. Furthermore, tumor inoculation nude mice model was used to explore the function of miR-206 in vivo. Our results showed that overexpression of miR-206 drastically inhibited tumor development. In summary, our data suggest that miR-206 inhibits HCC development by targeting PTP1B.
Highlights
Liver cancer, due to the high mortality rate, ranks the second place among all causes of cancer-related deaths [1]
We found that miR-206, which was down-regulated during tumorigenesis, inhibited the proliferation and invasion of Hepatocellular carcinoma (HCC) cells
The results showed that the expression of miR-206 was significantly down-regulated in all four HCC cell lines (Figure 1A)
Summary
Due to the high mortality rate, ranks the second place among all causes of cancer-related deaths [1]. Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high morbidity and mortality worldwide [2]. PTP1B (protein tyrosine phosphatase 1B) is a non-receptor-type oncogenic promoter involved in growth factor signaling [4]. Multiple reports found that PTP1B is up-regulated in several types of cancers, such as breast cancer, colorectal cancer, gastric cancer, and ovarian carcinomas, leading to enhanced invasion and migration of cancer cells [5,6,7,8]. Zheng et al reported that down-regulated expression of the PTP1B was associated with aggressive clinicopathologic features and poor prognosis in HCC [9]. The regulation of PTP1B in human HCC progression and invasion remains unclear
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