title: MicroRNA-135a contributes to the development of portal vein tumor thrombus by promoting metastasis in hepatocellular carcinoma.
abstract: OBJECTIVE
  Portal vein tumor thrombus (PVTT) has previously been demonstrated to correlate with poor prognosis of hepatocellular carcinoma. Approximately 50-80% of HCC is accompanied by portal or hepatic vein invasion. The underlying mechanisms of PVTT development remain unclear. This study aimed to elucidate the role of miR-135a in PVTT tumorigenesis.
  
  
  METHODS
  In the present study, we investigated the expression of microRNAs and mRNAs in PVTT tissues using advanced microRNA and cDNA microarray techniques. MicroRNA (miR)-135a was noted to be highly over-expressed in PVTT and the cell line CSQT-2 and was selected for further study. We characterized the function of miR-135a in vitro and in vivo. We also analyzed the clinical relevance of miR-135a in relation to the prognosis and survival of HCC patients with PVTT.
  
  
  RESULTS
  Our analyses found that the miRNA and mRNA expression profiles of PVTT were distinct from the parenchyma tumor. Overexpression of miR-135a favors invasive and metastatic behavior in vitro. Furthermore, in a CSQT-2 orthotopic transplantation nude mouse model, blockade of miR-135a significantly reduced PVTT incidence. We also found that miR-135a was transcribed by forkhead box M1 (FOXM1), and metastasis suppressor 1 (MTSS1) was identified as the direct and functional target of miR-135a. Additionally, the cohort analysis revealed the relevance of miR-135a with respect to the prognosis and survival of HCC patients with PVTT.
  
  
  CONCLUSIONS
  Our data suggest an important role for miR-135a in promoting PVTT tumorigenesis and indicate the potential application of miR-135a in PVTT therapy.
authors: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors: Shupeng
authors: S
authors: Liu
authors: Weixing
authors: W
authors: Guo
authors: Jie
authors: J
authors: Shi
authors: Nan
authors: N
authors: Li
authors: Xiya
authors: X
authors: Yu
authors: Jie
authors: J
authors: Xue
authors: Xiaohui
authors: X
authors: Fu
authors: Kaijian
authors: K
authors: Chu
authors: Chongde
authors: C
authors: Lu
authors: Jiangsha
authors: J
authors: Zhao
authors: Dong
authors: D
authors: Xie
authors: Mengchao
authors: M
authors: Wu
authors: Shuqun
authors: S
authors: Cheng
authors: Shanrong
authors: S
authors: Liu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000556:secondary*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D011169:Portal Vein; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D020246:Venous Thrombosis / Q000209:etiology*
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C544965:MIRN135 microRNA, human; C486778:MTSS1 protein, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm