The study supports the theory that cancer metastasis is a highly selective dynamic process and the cell model system could be a useful platform for the study of HCC metastasis.

(CHD1L) is a recently identified oncogene localized at 1q21, a frequently amplified region in hepatocellular carcinoma (HCC). To explore its oncogenic mechanisms, we set out to identify CHD1L-regulated genes using a chromatin immunoprecipitation-based (ChIP-based) cloning strategy in a human HCC cell line. We then further characterized 1 identified gene, ARHGEF9, which encodes a specific guanine nucleotide exchange factor (GEF) for the Rho small GTPase Cdc42. Overexpression of ARHGEF9 was detected in approximately half the human HCC samples analyzed and positively correlated with CHD1L overexpression. In vitro and in vivo functional studies in mice showed that CHD1L contributed to tumor cell migration, invasion, and metastasis by increasing cell motility and inducing filopodia formation and epithelial-mesenchymal transition (EMT) via ARHGEF9-mediated Cdc42 activation. Silencing ARHGEF9 expression by RNAi effectively abolished the invasive and metastatic abilities of CHD1L in mice. Furthermore, investigation of clinical HCC specimens showed that CHD1L and ARHGEF9 were markedly overexpressed in metastatic HCC tissue compared with healthy tissue. Increased expression of CHD1L was often observed at the invasive front of HCC tumors and correlated with venous infiltration, microsatellite tumor nodule formation, and poor disease-free survival. These findings suggest that CHD1L-ARHGEF9-Cdc42-EMT might be a novel pathway involved in HCC progression and metastasis.

Objective We investigated the awareness and acceptability of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and potential predicting factors. Methods This study was conducted among MSM in Beijing, China. Study participants, randomly selected from an MSM cohort, completed a structured questionnaire, and provided their blood samples to test for HIV infection and syphilis. Univariate logistic regression analyses were performed to evaluate the factors associated with willingness to accept (WTA) PrEP. Factors independently associated with willingness to accept were identified by entering variables into stepwise logistic regression analysis. Results A total of 152 MSM completed the survey; 11.2% had ever heard of PrEP and 67.8% were willing to accept it. Univariate analysis showed that age, years of education, consistent condom use in the past 6 months, heterosexual behavior in the past 6 months, having ever heard of PrEP and the side effects of antiretroviral drugs, and worry about antiretroviral drugs cost were significantly associated with willingness to accept PrEP. In the multivariate logistic regression model, only consistent condom use in the past 6 months (odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.13–0.70) and having ever heard of the side effects of antiretroviral drugs (OR: 0.30; 95% CI: 0.14–0.67) were independently associated with willingness to accept PrEP. Conclusions The awareness of PrEP in the MSM population was low. Sexual behavioral characteristics and knowledge about ART drugs may have effects on willingness to accept PrEP. Comprehensive prevention strategies should be recommended in the MSM community.

Background: The lncRNA LINC00460 plays crucial roles in several epithelial cancers, although its mechanisms of action differ greatly in different cellular contexts. In this study, we aimed to determine the potential clinical applications of LINC00460 and elucidate the mechanisms by which LINC00460 affects the development and progression of head and neck squamous cell carcinoma (HNSCC). Methods: The biological functions of LINC00460 were assessed in several epithelial cancer cell lines. The subcellular localization of LINC00460 was evaluated by cell nuclear/cytoplasmic fractionation and fluorescence in situ hybridization. RNA pull-down assays, LS-MS/MS analysis, and RNA and chromatin immunoprecipitation assays were performed to identify the molecular mechanism by which LINC00460 promotes HNSCC progression. The clinical pathological features of LINC00460 and PRDX1 were evaluated in HNSCC tissues and paired adjacent normal tissues. Results: LINC00460 enhanced HNSCC cell proliferation and metastasis in vitro and in vivo and induced epithelialmesenchymal transition (EMT). LINC00460 primarily localized within the cytoplasm of HNSCC cells, physically interacted with PRDX1 and facilitated PRDX1 entry into the nucleus. PRDX1 promoted the transcription of LINC00460, forming a positive feedback loop. In addition, PRDX1 also promoted the transcription of EMT-related genes (such as ZEB1, ZEB2 and VIM) through enrichment on gene promoters in the nucleus. LINC00460 effectively induced HNSCC cell EMT in a PRDX1-dependent manner, and PRDX1 mainly mediated the EMT-promoting effect of LINC00460. High levels of LINC00460 and PRDX1 expression were positively associated with lymph metastasis, pathological differentiation and tumor size in HNSCC patients. Conclusions: LINC00460 promoted EMT in HNSCC cells by facilitating PRDX1 entry into the nucleus. LINC00460 and PRDX1 are promising candidate prognostic predictors and potential targets for cancer therapy for HNSCC.