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PMID: 32068261 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Silencing of long noncoding RNA LEF1-AS1 prevents the progression of hepatocellular carcinoma via the crosstalk with microRNA-136-5p/WNK1.

Journal of cellular physiology ·Vol. 235 ·No. 10 ·2020-00-00 ·Pages 6548-6562

Dong H, Jian P, Yu M, Wang L

Abstract

Long noncoding RNAs (lncRNAs) have been recognized as cancer-associated biological molecules, favoring hepatocellular carcinoma (HCC) progression. This study was conducted to elucidate the effects lncRNA lymphoid enhancer-binding Factor 1 antisense RNA (LEF1-AS1) on the pathological development of HCC, along with the crosstalk involving microRNA-136-5p (miR-136-5p) and with-no-K (lysine) kinase 1 (WNK1). The study recruited primary HCC tissues and their corresponding nonneoplastic liver tissues. The gain- and loss-of-function studies were performed in HCC cells HuH-7 and tumor xenografts in nude mice. The dual luciferase reporter gene assay system, RNA pull-down, and radioimmunoprecipitation assays were applied to detect their interactions among lncRNA LEF1-AS1, miR-136-5p, and WNK1. 5-Ethynyl-2'-deoxyuridine staining, scratch test, Transwell assays, and in vitro tube formation assays were conducted to examine HCC cell proliferation, migration, and invasion and HUVEC angiogenesis. HCC tissues and cells contained high lncRNA LEF1-AS1 expression. LncRNA LEF1-AS1 upregulation triggered markedly increased HCC cell proliferation, migration, and invasion and human umbilical vein endothelial cell angiogenesis. In vivo silencing lncRNA LEF1-AS1 resulted in reduced tumor cell vitality and matrix metalloproteinase-9 and the vascular endothelial growth factor expression. Additionally, the role of lncRNA LEF1-AS1 was found to be largely dependent on WNK1. Association of lncRNA LEF1-AS1 with WNK1 blocked the inhibitory effect of miR-136-5p on WNK1, which was confirmed by in vivo experiments. Altogether, our results revealed an important role of lncRNA LEF1-AS1 in regulating the HCC progression by regulating WNK1, providing a potential biomarker for the therapeutic modalities regarding HCC.

Keywords
WNK1 hepatocellular carcinoma long noncoding RNA LEF1-AS1 microRNA-136-5p
MeSH Terms
Animals Carcinoma, Hepatocellular/genetics,pathology Cell Line Cell Line, Tumor Cell Movement/genetics Cell Proliferation/genetics Disease Progression Gene Expression Regulation, Neoplastic/genetics HEK293 Cells Human Umbilical Vein Endothelial Cells Humans Liver Neoplasms/genetics,pathology Lymphoid Enhancer-Binding Factor 1/genetics Mice Mice, Inbred BALB C Mice, Nude MicroRNAs/genetics Neovascularization, Pathologic/genetics,pathology RNA, Long Noncoding/genetics Vascular Endothelial Growth Factor A/genetics WNK Lysine-Deficient Protein Kinase 1/genetics
Chemicals
LEF1 protein, human Lymphoid Enhancer-Binding Factor 1 MIRN136 microRNA, human MicroRNAs RNA, Long Noncoding Vascular Endothelial Growth Factor A WNK Lysine-Deficient Protein Kinase 1 WNK1 protein, human
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Dong Hui
Center of Research Equipment Management, General Hospital of Ningxia Medical University, Yinchuan, China.
Jian Peng
Center of Research Equipment Management, General Hospital of Ningxia Medical University, Yinchuan, China.
Yu Mengchu
Center of Research Equipment Management, General Hospital of Ningxia Medical University, Yinchuan, China.
Wang Lixin ORCID
Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, China.
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Article Info
Journal
Journal of cellular physiology
Abbr.
J Cell Physiol
ISSN
1097-4652
DOI
10.1002/jcp.29503
Published
2020-00-00
Epub
2020-00-18
Pages
6548-6562
Language
English
Region
United States
NLM ID
0050222
Subset
IM
External Links
PubMed source DOI: 10.1002/jcp.29503 View journal details
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