Although epithelial membrane protein 3 (EMP3) has been implicated as a candidate tumor suppressor gene for low grade glioma, its biological function in glioblastoma multiforme (GBM) still remains poorly understood. Herein, we showed that EMP3 was highly expressed in CD44-high primary GBMs. Depletion of EMP3 expression suppressed cell proliferation, impaired in vitro tumorigenic potential and induced apoptosis in CD44-high GBM cell lines. We also identified TGF-β/Smad2/3 signaling pathway as a potential target of EMP3. EMP3 interacts with TGF-βreceptor type 2 (TGFBR2) upon TGF-βstimulation in GBM cells. Consequently, the EMP3-TGFBR2 interaction regulates TGF-β/Smad2/3 signaling activation and positively impacts on TGF-βstimulated gene expression and cell proliferation in vitro and in vivo. Highly correlated protein expression of EMP3 and TGF-β/Smad2/3 signaling pathway components was also observed in GBM specimens, confirming the clinical relevancy of activated EMP3/TGF-β/Smad2/3 signaling in GBM. In conclusion, our findings revealed that EMP3 might be a potential target for CD44-high GBMs and highlight the essential functions of EMP3 in TGF-β/Smad2/3 signaling activation and tumor progression.

Abstract. Hepatocellular carcinoma (HCC) is a highly malignant tumor and can evolve rapidly to resistance to chemotherapies. Glycochenodeoxycholate (GCDA), which is toxic and hydrophobic, is the main ingredient in the bile and associated with carcinogenesis of gastrointenstinal tumors. Bcl-2 is the most important anti-apoptotic protein and overexpressed in various human tumors. In the present study, we found that GCDA can induce the chemoresistance of human liver cancer cells and specific depletion of Bcl-2 by RNA interference blocks GCDA-stimulated chemoresistance, which indicate the pivotal role of Bcl-2 in such process. Mechanistically, GCDA simultaneously stimulates phosphorylation of Bcl-2 at Ser70 site and activates extracellular signal-regulated kinase 1/2 (ERK1/2), and inhibition of ERK1/2 by PD98059 (MAPK/ERK1/2 inhibitor) or siRNA (targeting ERK1/2) suppresses GCDA-stimulated phosphorylation of Bcl-2 and significantly attenuates the survival and chemoresistance induced by GCDA in liver cancer cells. Thus, GCDA-induced survival and chemoresistance of liver cancer cells may occur through activation of Bcl-2 by phosphorylation at Ser70 site through MAPK/ERK1/2 pathway, which may contribute to the development of human liver cancer and chemoresistance.

Psoriasis is a common, chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and increased blood flow induced by the stimulation of tissueresident immune cells by markedly altered cutaneous cytokine profiles. 1 Psoriasis affects approximately 2% of the general population. 2 It is a complex, multifactorial disease. Genetic as well as environmental factors contribute to the susceptibility and severity of psoriasis. Although the multifactorial etiology of psoriasis is well established, family and twin studies indicate a strong genetic component. 3 During the past five years, genome-wide association studies (GWAS), primarily based on single nucleotide polymorphism markers, have identified many loci as potential psoriasis susceptibility regions. 4,5 Angiotensin-converting enzyme (ACE) is an important circulating enzyme in the renin-angiotensin-aldosterone system (RAAS). 6 ACE is expressed in a wide range of tissues including skin, vascular endothelium and immune cells. The relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and psoriasis has previously been studied mainly in Caucasians and only once in Asians. The aim of this study is to evaluate the association between the ACE I/D polymorphism and the risk of psoriasis in a Chinese population. Materials and methods:The study population consisted of 668 psoriasis patients and 668 matched control subjects. The ACE I/D gene polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results:The frequency of the ACE II genotype (odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.06, 1.63; P = 0.01) and I allele (OR = 1.25, 95% CI = 1.06, 1.48; P = 0.01) in patients with psoriasis was significantly higher than that in the control group. And the D allele frequency in patients with psoriasis was significantly lower (OR = 0.80, 95% CI = 0.68, 0.95; P = 0.01) than that in the control group. When stratified by family history, the frequency of the DD genotype was marginally significantly lower in patients with a positive family history of psoriasis (familial psoriasis) than in those with negative (sporadic psoriasis) (OR = 0.47, 95% CI = 0.23, 0.97; P = 0.04). When stratified by onset of the disease, type of psoriasis and the severity of psoriasis, no statistically significant result was observed. Conclusion: Our study suggested that the ACE II genotype and I allele might confer susceptibility to psoriasis in a Chinese population.