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.
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.


CONCLUSIONS
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.
Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Sheng-Xian
SX
Yuan
Fu
F
Yang
Yuan
Y
Yang
Qi-Fei
QF
Tao
Jin
J
Zhang
Gang
G
Huang
Yun
Y
Yang
Ruo-Yu
RY
Wang
Sen
S
Yang
Xi-Song
XS
Huo
Ling
L
Zhang
Fang
F
Wang
Shu-Han
SH
Sun
Wei-Ping
WP
Zhou
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010735:Phosphoglycerate Kinase / Q000097:blood / Q000378:metabolism*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D062085:RNA, Long Noncoding / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics; D012307:Risk Factors; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000378:metabolism
D062085:RNA, Long Noncoding; C489053:RPS24 protein, human; D012269:Ribosomal Proteins; D000509:alpha-Fetoproteins; C577282:PGK1 protein, human; C528165:Pgk1 protein, mouse; D010735:Phosphoglycerate Kinase