Abstract
BackgroundmiR-199a-3p was significantly downregulated in the majority of human hepatocellular carcinoma (HCC) tissues and HCC cell lines. Yes associated protein 1 (YAP1) was overexpressed in human HCC, which promoted HCC development and progression by upregulating Jagged1 and activating the Notch pathway. We searched potential targets of miR-199a-3p with DIANA, TargetScan and PicTar tools, and found that YAP1 is one of the potential targets. Based on these findings, we speculated that miR-199a-3p might suppress HCC growth by targeting YAP1, downregulating Jagged1 and suppressing the Notch pathway.ResultsWe determined the expression of miR-199a-3p and YAP1 by quantitative Real-Time PCR (qRT-PCR) and western blot assays, respectively, and found downregulation of miR-199a-3p and upregulation of YAP1 in HCC cell lines. Cell proliferation and apoptosis assays showed that miR-199a-3p suppresses HCC cell proliferation and promotes apoptosis, and knockdown of YAP1 has similar role. Furthermore, we verified that miR-199a-3p can directly target YAP1. We further investigated and confirmed that miR-199a-3p and YAP1 regulate HCC cell proliferation and apoptosis through Jagged1-Notch signaling.ConclusionmiR-199a-3p targets YAP1, downregulates Jagged1 and suppresses the Notch signaling to inhibit HCC cell proliferation and promote apoptosis. These findings provide new insights into the mechanism by which miR-199a-3p suppresses HCC cell proliferation and induces apoptosis.
Highlights
MiR-199a-3p was significantly downregulated in the majority of human hepatocellular carcinoma (HCC) tissues and HCC cell lines
Results miR-199a-3p was downregulated and Yes associated protein 1 (YAP1) was upregulated in HCC cell lines miR-199a-3p expression was determined in five human HCC cell lines (MHCC97H, Hep3B, Huh7, SMMC-7721 and HepG2) and a normal liver cell line (HL-7702) by quantitative Real-Time PCR (qRT-PCR)
The results showed that the expression of miR-199a-3p in HCC cell lines was very lower than that in HL-7702 cells (Fig. 1a)
Summary
MiR-199a-3p was significantly downregulated in the majority of human hepatocellular carcinoma (HCC) tissues and HCC cell lines. Yes associated protein 1 (YAP1) was overexpressed in human HCC, which promoted HCC development and progression by upregulating Jagged and activating the Notch pathway. We searched potential targets of miR-199a-3p with DIANA, TargetScan and PicTar tools, and found that YAP1 is one of the potential targets Based on these findings, we speculated that miR-199a-3p might suppress HCC growth by targeting YAP1, downregulating Jagged and suppressing the Notch pathway. Increasing evidence shows that there exist causal relationship between the deregulation of miRNA expression and the initiation and development of cancer, and miRNAs can play oncogenic or tumor suppressive roles in human cancers depending on the target genes [10]. Many dysregulated miRNAs have been reported to play important roles in the occurrence and progression of HCC, and miRNAs have been suggested as potential biomarkers and novel therapeutic targets for HCC [11, 12]
Sign-in/Register to view highlights & summary 
Published Version
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 call