Abstract
Alpha fetoprotein (AFP) is a clinical biomarker of hepatocellular carcinoma (HCC). Here, we found that miR-1236 is down-regulated, whereas AFP is highly expressed in HCC tissues and cells. We demonstrated that miR-1236 directly targets the 3'UTR of AFP and down-regulates its expression. Also, miR-1236 inhibited and AFP stimulated proliferation, migration, invasion and vasculogenic mimicry (VM) of HCC. In agreement, AFP over-expression counteracted the inhibitory effect of miR-1236. We demonstrated that AFP promoted the ubiquitination of PTEN, thus decreasing PTEN levels, while miR-1236 inhibited the PI3K/Akt pathway.
Keywords:
AFP; PTEN; hepatocellular cancer; microRNA; microRNA-1236.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Carcinoma, Hepatocellular / genetics
-
Carcinoma, Hepatocellular / metabolism*
-
Cell Line, Tumor
-
Cell Proliferation
-
Down-Regulation
-
Female
-
HEK293 Cells
-
Hep G2 Cells
-
Humans
-
Liver Neoplasms / genetics
-
Liver Neoplasms / metabolism*
-
Mice
-
Mice, Nude
-
MicroRNAs / genetics
-
MicroRNAs / metabolism*
-
PTEN Phosphohydrolase / genetics
-
PTEN Phosphohydrolase / metabolism*
-
Phenotype
-
Phosphatidylinositol 3-Kinases / metabolism*
-
Proto-Oncogene Proteins c-akt / metabolism*
-
Signal Transduction
-
Transfection
-
alpha-Fetoproteins / metabolism*
Substances
-
AFP protein, human
-
MIRN1236 microRNA, human
-
MicroRNAs
-
alpha-Fetoproteins
-
Phosphatidylinositol 3-Kinases
-
Proto-Oncogene Proteins c-akt
-
PTEN Phosphohydrolase
-
PTEN protein, human