ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. P21-activated kinase 4 (PAK4) has been identified as an oncogenic protein in a variety of cancers. However, the contribution and regulation of PAK4 in HCC remain poorly understood. In the present study, we found that inhibition of PAK4 expression by specific shRNA significantly attenuated HCC cell proliferation. Moreover, we show that microRNA-433 (miRNA-433) could directly target PAK4 through the miRNA-433 binding sequence at the 3'-UTR of PAK4 mRNA, and inhibit PAK4 protein expression. We further show that miRNA-433 expression was downregulated in HCC tissues and cell culture as well, which inversely correlated with PAK4 expression levels. Overexpression of miRNA-433 significantly suppressed the proliferation of HepG2 cells, while this effect was partially rescued by forced expression of PAK4 through restoring PI3K/AKT signaling in HepG2 cells. These findings will shed light on the roles and mechanisms of miRNA-433 in regulating HCC proliferation, and may benefit future development of therapeutics targeting miRNA-433 and PAK4 in HCC.
Subject(s)
Carcinoma, Hepatocellular/enzymology , Liver Neoplasms/enzymology , MicroRNAs/genetics , p21-Activated Kinases/genetics , 3' Untranslated Regions , Base Sequence , Binding Sites , Carcinoma, Hepatocellular/genetics , Cell Proliferation , Down-Regulation , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA Interference , Signal Transduction , p21-Activated Kinases/metabolismABSTRACT
We assessed whether red cell distribution width (RDW) is associated with serum uric acid (UA) level in a group of 512 patients with newly diagnosed hypertension, recruited in Beijing. Patients were divided into high uric acid group and low uric acid group according to the median (334.9 µmol/L) of serum uric acid. Compared with the low uric acid group, the patients with high uric acid had higher red blood cell count (P < 0.001) and RDW (P = 0.032). The multiple linear regression analysis showed that RDW (P = 0.001) was positively correlated with uric acid level after the adjustment of related factors. Stepwise multiple logistic regression model confirmed that RDW (odds ratio: OR = 1.75) was independent determinants of high serum uric acid as well as sex (OR = 6.03), triglycerides (OR = 1.84), and Blood Urea Nitrogen (BUN, OR = 1.30). RDW may be independently associated with serum UA level in patients with newly diagnosed hypertension. To firmly establish the causal role of RDW in the incidence of high uric acid level among hypertensive patients, large cohort studies are needed.
