Long noncoding RNA n339260 promotes vasculogenic mimicry and cancer stem cell development in hepatocellular carcinoma.

Abstract

Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. Cancer stem cells (CSC) represent a subpopulation of tumor cells endowed with the capacity for self-renewal and multilineage differentiation. Previous studies have indicated that CSC may participate in the formation of VM. With the advance of high-resolution microarrays and massively parallel sequencing technology, long noncoding RNAs (lncRNAs) are suggested to play a critical role in tumorigenesis and, in particular, the development of human hepatocellular carcinoma (HCC). Currently, no definitive relationship between lncRNA and VM formation has been described. In the current study, we demonstrated that expression of the lncRNA, n339260, is associated with CSC phenotype in HCC, and n339260 level correlated with VM, metastasis, and shorter survival time in an animal model. Overexpression of n339260 in HepG2 cells was associated with a significant increase in CSC. Additionally, the appearance of VM and vascular endothelial (VE)-cadherin, a molecular marker of VM, was also induced by n339260 overexpression. Using a short hairpin RNA approach, n339260 was silenced in tumor cells, and knockdown of n339260 was associated with reduced VM and CSC. The results of this study indicate that n339260 promotes VM, possibly by the development of CSC. The related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis.

• Authors: Xiulan Zhao, Baocun Sun, Tieju Liu, Bing Shao, Ran Sun, Dongwang Zhu, Yanhui Zhang, Qiang Gu, Xueyi Dong, Fang Liu, Nan Zhao, Danfang Zhang, Yanlei Li, Jie Meng, Wenchen Gong, Yanjun Zheng, Xu Zheng
• Journal: Cancer science (Cancer Sci) Vol. 109 Issue 10 Pg. 3197-3208 (Oct 2018) ISSN: 1349-7006 [Electronic] England
• PMID: 30022558 (Publication Type: Journal Article)
• Copyright: © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• RNA, Long Noncoding
• RNA, Small Interfering

Topics

• Animals
• Carcinoma, Hepatocellular (blood supply, genetics, mortality, pathology)
• Cell Differentiation (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Hep G2 Cells
• Hepatectomy
• Humans
• Liver (pathology, surgery)
• Liver Neoplasms (blood supply, genetics, mortality, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplastic Stem Cells (pathology)
• Neovascularization, Pathologic (genetics, mortality, pathology)
• RNA, Long Noncoding (genetics, metabolism)
• RNA, Small Interfering (metabolism)
• Spheroids, Cellular
• Xenograft Model Antitumor Assays