Abstract
The expression and function of microRNA-638 (miR-638) in hepatocellular carcinoma (HCC) remained unknown. Using the miRNA target prediction tools, we predicted that the vascular endothelial growth factor (VEGF) might be a direct target of miR-638. The aim of this study was to test the hypothesis that downregulation of miRNA-638 promotes angiogenesis and growth of HCC by targeting the VEGF signaling pathway. We found that miR-638 was significantly downregulated in HCC cells and clinical HCC specimens, and miR-638 levels were inversely correlated with tumor size, portal vein invasion and poor prognosis. Overexpression of miR-638 inhibited the processes of tumor angiogenesis in vitro and in vivo. The xenograft mouse model experiments showed miR-638 repressed tumor growth of HCC in vivo. Using a luciferase reporter assay, we identified VEGF as a direct target of miR-638. Subsequent investigation revealed that miR-638 expression was inversely correlated with VEGF expression in human HCC samples. Taken together, these results suggested that miR-638 is a novel therapeutic target for HCC and overexpression of miR-638 could suppress angiogenesis and tumor growth of HCC by inhibiting VEGF signaling.
Highlights
Active angiogenesis and metastasis are responsible for rapid recurrence and poor survival of patients with hepatocellular carcinoma (HCC) [1]
We found that clinical HCC samples have lower levels of vascular endothelial growth factor (VEGF) protein in tumor tissues than those in adjacent non-tumor tissues from the same patient (Figure 3A), and the VEGF protein levels miR-638 levels were inversely correlated with VEGF levels (r = −0.793, P < 0.001, Figure 3B)
Dysregulation of miR-638 has been described in several different types of human tumors, including human gastric cancer [6], basal cell carcinoma [7], breast cancer [8], nonsmall-cell lung cancer [9], colorectal carcinoma [10] and chronic lymphocytic leukemia [11]
Summary
Active angiogenesis and metastasis are responsible for rapid recurrence and poor survival of patients with hepatocellular carcinoma (HCC) [1]. MiR-638 was significantly downregulated and may play a cancer suppressing role in human gastric cancer [6], basal cell carcinoma [7], breast cancer [8], non-small cell lung cancer [9], colorectal carcinoma [10], and chronic lymphocytic leukemia [11]. A recent study reported that the expression of miR-638 was higher in liver cancer tissues than normal liver tissues [16]. The above evidence suggests that miR-638 may play an important role in tumorigenesis and tumor progression, the expression and functional role of miR-638 in HCC remained largely unknown. We hypothesized that downregulation of miRNA-638 promotes angiogenesis and growth of hepatocellular carcinoma by targeting the VEGF signaling pathway.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
