Niclosamide inhibited vascular smooth muscle cell proliferation and migration and attenuated neointimal hyperplasia in balloon-injured rat carotid arteries through a mechanism involving inhibition of STAT3.

No abstract

Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein. We had reported that CPEB3 is involved in hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of CPEB3 in HCC remain unclear. In this study, we firstly performed RNA immunoprecipitation to uncover the transcriptome-wide CPEB3-bound mRNAs (CPEB3 binder) in HCC. Bioinformatic analysis indicates that CPEB3 binders are closely related to cancer progression, especially HCC metastasis. Further studies confirmed that metadherin (MTDH) is a direct target of CPEB3. CPEB3 can suppress the translation of MTDH mRNA in vivo and in vitro. Besides, luciferase assay demonstrated that CPEB3 interacted with 3′-untranslated region of MTDH mRNA and inhibited its translation. Subsequently, CPEB3 inhibited the epithelial–mesenchymal transition and metastasis of HCC cells through post-transcriptional regulation of MTDH. In addition, cpeb3 knockout mice are more susceptible to carcinogen-induced hepatocarcinogenesis and subsequent lung metastasis. Our results also indicated that CPEB3 was a good prognosis marker, which is downregulated in HCC tissue. In conclusion, our results demonstrated that CPEB3 played an important role in HCC progression and targeting CPEB3-mediated mRNA translation might be a favorable therapeutic approach.

This study aimed to investigate the effect of miR-671-5p on metastasis of clear cell renal cell carcinoma (ccRCC) and underlying mechanism involved. The migration and invasion of ccRCC cells were determined by transwell and boyden assays in vitro and in vivo. Genes mRNA and protein expression were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The target gene of miRNA was confirmed by luciferase reporter assays. Transcriptional regulation of miRNA by transcription factor was detected by chromatin immunoprecipitation assay (ChIP). The expressions of miRNA in clinical specimens were detected by in situ hybridization (ISH). miR-671-5p promoted migration and invasion of ccRCC in vivo and in vitro. Moreover, miR-671-5p directly targeted APC to activate Wnt signaling, thus inducing the epithelial-mesenchymal transition (EMT) in ccRCC. Intriguingly, miR-671-5p expression was transcriptionally enhanced by HMGA1. Consistently, bioinformatics analysis suggested that HMGA1 was positively correlated with miR-671 expression; however, miR-671 was negatively correlated with APC. In situ hybridization analysis showed that miR-671-5p was upregulated in ccRCC compared with paracarcinoma and correlated with poor prognosis of ccRCC patients. In addition, univariate and multivariate analysis indicated that miR-671-5p expression was an independent prognostic factor for overall survival in ccRCC patients. Our data suggest that miR-671-5p is a tumor enhancer in regulating of ccRCC metastasis, and miR-671-5p may be utilized as a factor for the clinical diagnosis and prognosis of ccRCC.