Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients' poor recurrence-free survival after hepatectomy.

Abstract

UNLABELLED:

Survival of patients with hepatocellular carcinoma (HCC) remains poor, which is largely attributed to active angiogenesis. However, the mechanisms underlying angiogenesis in HCC remain to be discovered. In this study, we found that long noncoding RNA associated with microvascular invasion in HCC (lncRNA MVIH) (lncRNA associated with microvascular invasion in HCC) was generally overexpressed in HCC. In a cohort of 215 HCC patients, the overexpression of MVIH was associated with frequent microvascular invasion (P = 0.016) and a higher tumor node metastasis stage (P = 0.009) as well as decreased recurrence-free survival (RFS) (P < 0.001) and overall survival (P = 0.007). Moreover, the up-regulation of MVIH served as an independent risk factor to predict poor RFS. We also found that MVIH could promote tumor growth and intrahepatic metastasis by activating angiogenesis in mouse models. Subsequent investigations indicated that MVIH could activate tumor-inducing angiogenesis by inhibiting the secretion of phosphoglycerate kinase 1 (PGK1). Additionally, in 65 HCC samples, MVIH expression was inversely correlated with the serum level of PGK1 and positively correlated with the microvessel density.

CONCLUSION:

Deregulation of lncRNA MVIH is a predictor for poor RFS of HCC patients after hepatectomy and could be utilized as a potential target for new adjuvant therapies against active angiogenesis.

• Authors: Sheng-Xian Yuan, Fu Yang, Yuan Yang, Qi-Fei Tao, Jin Zhang, Gang Huang, Yun Yang, Ruo-Yu Wang, Sen Yang, Xi-Song Huo, Ling Zhang, Fang Wang, Shu-Han Sun, Wei-Ping Zhou
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 56 Issue 6 Pg. 2231-41 (Dec 2012) ISSN: 1527-3350 [Electronic] United States
• PMID: 22706893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Association for the Study of Liver Diseases.

Chemical References

• RNA, Long Noncoding
• RPS24 protein, human
• Ribosomal Proteins
• alpha-Fetoproteins
• PGK1 protein, human
• Pgk1 protein, mouse
• Phosphoglycerate Kinase

Topics

• Animals
• Carcinoma, Hepatocellular (blood supply, genetics, pathology)
• Cell Line, Tumor
• Disease-Free Survival
• Female
• Gene Expression
• Hepatectomy
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms (blood supply, genetics, pathology)
• Male
• Mice
• Microvessels (pathology)
• Middle Aged
• Neoplasm Invasiveness
• Neovascularization, Pathologic (genetics)
• Phosphoglycerate Kinase (blood, metabolism)
• Predictive Value of Tests
• Proportional Hazards Models
• RNA, Long Noncoding (genetics)
• Ribosomal Proteins (genetics)
• Risk Factors
• Up-Regulation
• alpha-Fetoproteins (metabolism)