Back to Search
Start Over
Targeting protein arginine methyltransferase 5 inhibits human hepatocellular carcinoma growth via the downregulation of beta-catenin.
- Source :
-
Journal of translational medicine [J Transl Med] 2015 Nov 05; Vol. 13, pp. 349. Date of Electronic Publication: 2015 Nov 05. - Publication Year :
- 2015
-
Abstract
- Background: Protein arginine methyltransferase 5 (PRMT5), a type II PRMT, is highly expressed in some tumors, but its role in hepatocellular carcinoma (HCC) is still unknown.<br />Methods: PRMT5 level in HCC specimens was determined by immunohistochemical staining and the association with clinicopathologic features was evaluated. PRMT5 was inhibited by AMI-1 (a small molecule inhibitor of PRMTs) or small interference RNA (siRNA). The proliferation of HCC cells was tested by Cell Counting Kit-8, cell migration was evaluated by Transwell assay and cell cycle and apoptosis were analyzed by flow cytometry. The effect of AMI-1 on HCC in vivo was examined by mouse xenograft model.<br />Results: PRMT5 expression was markedly upregulated in HCC tissues, and correlated inversely with overall patient survival. Knockdown of PRMT5 significantly reduced the proliferation of HCC cells, but did not affect the growth of normal liver cells. Furthermore, β-catenin was identified as a target of PRMT5. Silencing PRMT5 significantly down-regulated the expression of β-catenin and the downstream effector Cyclin D1 in HCC cells. AMI-1 strongly inhibited HCC growth in vivo, increased the ratio of Bax/Bcl-2, and led to apoptosis and loss of migratory activity in several HCC cells. Meanwhile, AMI-1 decreased the expression levels of symmetric dimethylation of H4 (H4R3me2s), a histone mark of PRMT5.<br />Conclusions: PRMT5 plays an important role in HCC. PRMT5 may be a promising target for HCC therapy.
- Subjects :
- Animals
Apoptosis
Cell Cycle
Cell Line, Tumor
Cell Movement
Cell Proliferation
Down-Regulation
Female
Flow Cytometry
Gene Silencing
Humans
Immunohistochemistry
Male
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Protein-Arginine N-Methyltransferases metabolism
RNA Interference
RNA, Small Interfering metabolism
Rats
Urea pharmacology
Carcinoma, Hepatocellular metabolism
Gene Expression Regulation, Neoplastic
Liver Neoplasms metabolism
Naphthalenesulfonates pharmacology
Protein-Arginine N-Methyltransferases antagonists & inhibitors
Urea analogs & derivatives
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1479-5876
- Volume :
- 13
- Database :
- MEDLINE
- Journal :
- Journal of translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 26541651
- Full Text :
- https://doi.org/10.1186/s12967-015-0721-8