miR-199a-3p inhibits cell proliferation and induces apoptosis by targeting YAP1, suppressing Jagged1-Notch signaling in human hepatocellular carcinoma.
BACKGROUND
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 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.


RESULTS
We 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.


CONCLUSIONS
miR-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.
Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China. rkwzzu@163.com.|Interventional Institute of Zhengzhou University, Zhengzhou, 450052, People's Republic of China. rkwzzu@163.com.|Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, 450052, People's Republic of China. rkwzzu@163.com.
Kewei
http://orcid.org/0000-0001-7930-6966
K
Ren
Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China.|Interventional Institute of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.|Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, 450052, People's Republic of China.
Tengfei
T
Li
Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China.|Interventional Institute of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.|Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, 450052, People's Republic of China.
Wenzhe
W
Zhang
Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China.|Interventional Institute of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.|Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, 450052, People's Republic of China.
Jianzhuang
J
Ren
Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China.|Interventional Institute of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.|Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, 450052, People's Republic of China.
Zhen
Z
Li
Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China.|Interventional Institute of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.|Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, 450052, People's Republic of China.
Gang
G
Wu
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000072100:Jagged-1 Protein / Q000096:biosynthesis / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D051880:Receptors, Notch / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D000072100:Jagged-1 Protein; D035683:MicroRNAs; D010750:Phosphoproteins; D051880:Receptors, Notch; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C531408:mirn199 microRNA, human
Hepatocellular carcinoma; Jagged1; Notch signaling; Yes associated protein 1; miR-199a-3p