Research Paper Volume 11, Issue 20 pp 9111—9127

Long noncoding RNA HULC promotes hepatocellular carcinoma progression

Hongwei Zhang 1, 2, *, , Zhibin Liao 1, 2, *, , Furong Liu 1, 2, *, , Chen Su 1, 2, , He Zhu 1, 2, , Yani Li 1, 2, , Ran Tao 1, 2, , Huifang Liang 1, 2, , Bixiang Zhang 1, 2, , Xuewu Zhang 1, 2, ,

  • 1 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
  • 2 Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan 430030, Hubei, China
* Equal contribution

received: July 1, 2019 ; accepted: October 14, 2019 ; published: October 23, 2019 ;

https://doi.org/10.18632/aging.102378
How to Cite

Copyright © 2019 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Long noncoding RNAs (lncRNAs) are overexpressed in many types of cancers, suggesting they may promote tumorigenesis. The lncRNA “highly upregulated in liver cancer” (HULC) promotes hepatocellular carcinoma (HCC) by mechanisms that are not fully understood. In the present study, we showed that HULC is overexpressed in HCC tissues, which correlates with an unfavorable prognosis in HCC patients. We also found that HULC promotes the proliferation, migration, and invasion of HCC cells in vitro, and xenograft tumor growth in vivo. Our mechanistic studies showed that HULC works as a competing endogenous RNA for miR-2052, and that the MET receptor tyrosine kinase is a downstream target of miR-2052 in HCC. Furthermore, HULC inhibits miR-2052, thereby stimulating MET expression in HCC. Finally, MET overexpression reverses the effects of HULC depletion. In sum, our findings reveal a novel regulatory signaling cascade, the HULC/miR-2052/MET axis, which could potentially be exploited for therapeutic benefits in the treatment of HCC.

Abbreviations

LncRNAs: long noncoding RNAs; ceRNA: competing endogenous RNA; IgG: immunoglobulin G; qPCR: quantitative real-time polymerase chain reaction; miRNA: microRNA; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; HE: hematoxylin-eosin.