Role of mir-148a in hepatitis B associated hepatocellular carcinoma
dc.creator | Yuan, K | |
dc.creator | Lian, Z | |
dc.creator | Sun, B | |
dc.creator | Clayton, MM | |
dc.creator | Ng, IOL | |
dc.creator | Feitelson, MA | |
dc.date.accessioned | 2021-01-31T22:29:17Z | |
dc.date.available | 2021-01-31T22:29:17Z | |
dc.date.issued | 2012-04-09 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.doi | http://dx.doi.org/10.34944/dspace/5451 | |
dc.identifier.other | 22496917 (pubmed) | |
dc.identifier.uri | http://hdl.handle.net/20.500.12613/5469 | |
dc.description.abstract | Hepatitis B virus encoded X antigen (HBx) is a trans-regulatory protein that alters the activity of selected transcription factors and cytoplasmic signal transduction pathways. HBx transcriptionally up-regulates the expression of a unique gene, URG11, which in turn transcriptionally up-regulates β-catenin, thereby contributing importantly to hepatocarcinogenesis. HBx and URG11 also alter the expression of multiple microRNAs, and by miRNA array analysis, both were shown to promote the expression of miR-148a. Elevated miR-148a was also seen in HBx positive liver samples from infected patients. To study the function of miR-148a, anti-148a was introduced into HepG2 and Hep3B cells stably expressing HBx or stably over-expressing URG11. Anti-miR-148a suppressed cell proliferation, cell cycle progression, cell migration, anchorage independent growth in soft agar and subcutaneous tumor formation in SCID mice. Introduction of anti-miR-148a increased PTEN protein and mRNA expression, suggesting that PTEN was targeted by miR-148a. Anti-miR-148a failed to suppress PTEN expression when co-transfected with reporter gene mutants in the 3′UTR of PTEN mRNA. Introduction of anti-miR-148a also resulted in depressed Akt signaling by HBx and URG11, resulting in decreased expression of β-catenin. Thus, miR-148a may play a central role in HBx/URG11 mediated HCC, and may be an early diagnostic marker and/or therapeutic target associated with this tumor type. © 2012 Yuan et al. | |
dc.format.extent | e35331-e35331 | |
dc.language.iso | en | |
dc.relation.haspart | PLoS ONE | |
dc.relation.isreferencedby | Public Library of Science (PLoS) | |
dc.rights | CC BY | |
dc.subject | 3' Untranslated Regions | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Animals | |
dc.subject | Carcinoma, Hepatocellular | |
dc.subject | Cell Cycle | |
dc.subject | Cell Line, Tumor | |
dc.subject | Cell Movement | |
dc.subject | Cell Proliferation | |
dc.subject | Female | |
dc.subject | Hepatitis B | |
dc.subject | Humans | |
dc.subject | Liver Neoplasms | |
dc.subject | Male | |
dc.subject | Mice | |
dc.subject | Mice, SCID | |
dc.subject | MicroRNAs | |
dc.subject | Middle Aged | |
dc.subject | PTEN Phosphohydrolase | |
dc.subject | Proto-Oncogene Proteins c-akt | |
dc.subject | Trans-Activators | |
dc.subject | Viral Regulatory and Accessory Proteins | |
dc.subject | beta Catenin | |
dc.title | Role of mir-148a in hepatitis B associated hepatocellular carcinoma | |
dc.type | Article | |
dc.type.genre | Journal Article | |
dc.relation.doi | 10.1371/journal.pone.0035331 | |
dc.ada.note | For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu | |
dc.date.updated | 2021-01-31T22:29:12Z | |
refterms.dateFOA | 2021-01-31T22:29:17Z |