title: MicroRNA-155-5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway.
abstract: MicroRNA-155-5p (miR-155-5p) has been reported to play an oncogenic role in different human malignancies; however, its role in hepatocellular carcinoma (HCC) progression is not clearly understood. In this study, we used real-time PCR in 20 rats with chemically-induced HCC, 28 human HCC tissues, and the matched paracarcinoma tissues, and HCC cell lines to determine the expression patterns of miR-155-5p and PTEN mRNA. Algorithm-based and experimental strategies, such as dual luciferase gene reporter assays, real-time PCR and western blots were used to identify PTEN as a candidate miR-155-5p target. Gain- and loss-of-function experiments and administration of a PI3K/Akt pathway inhibitor (wortmannin) were used to identify the effects of miR-155-5p and PTEN in MTT assays, flow cytometric analysis, wound healing assays and transwell assays. The results showed that miR-155-5p was highly overexpressed; however, PTEN was underexpressed in the HCC rat models, human HCC tissues and cell lines. In addition, miR-155-5p upregulation and PTEN downregulation were significantly associated with TNM stage (P < 0.05). Through in vitro experiments, we found that miR-155-5p promoted proliferation, invasion and migration, but inhibited apoptosis in HCC by directly targeting the 3'-UTR of PTEN. Western blots showed that miR-155-5p inactivated Bax and caspase-9, but activated Bcl-2 to inhibit apoptosis, and it activated MMP to promote migration and invasion via the PI3K/Akt pathway. A xenograft tumor model was used to demonstrate that miR-155-5p targets PTEN and activates the PI3K/Akt pathway in vivo as well. Our study highlighted the importance of miR-155-5p and PTEN associated with aggressive HCC both in vitro and in vivo.
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Department of Respiratory, Third Hospital of Xi'an, Xi'an, Shaanxi, China.
authors.forename: Hongqing
authors.initials: H
authors.lastname: Wen
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.affiliation: The third Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Kejun
authors.initials: K
authors.lastname: Nan
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tian
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: 
  PTEN
  ; Hepatocellular carcinoma; PI3K/Akt pathway; hepatocellular carcinoma progression; microRNA-155-5p