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Background: The budding uninhibited by benzimidazoles (BUB) family is involved in the cell cycle process as mitotic checkpoint components. Abnormal proliferation is a vital process in the development of lung adenocarcinoma (LUAD). Nevertheless, the roles of BUB1 in LUAD remain unclear. In this study, we evaluated the prognostic value and biological functions of BUB1 in LUAD using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), clinical LUAD samples, and in vitro experiments. Methods: The expression, prognostic significance, functions, immune infiltration, and methylation of BUB1 in LUAD were comprehensively analyzed using TCGA, GEO, Gene Expression Profiling Interactive Analysis, Metascape, cBioPortal, MethSurv, and cancerSEA databases. Furthermore, we performed a battery of in vitro experiments and immunohistochemistry (IHC) to verify the bioinformatics results. Results: Multivariate analysis revealed that BUB1 overexpression was an independent prognostic factor (hazard ratio = 1.499, p = 0.013). Functional enrichment analysis showed that BUB1 was correlated with cell cycle, proliferation, DNA repair, DNA damage, and invasion (p < 0.05). Finally, in vitro experiments showed that downregulation of BUB1 inhibited the proliferation, migration, and invasion of LUAD cells and promoted LUAD cell apoptosis. IHC also showed that BUB1 was overexpressed in LUAD (p < 0.001) and was significantly associated with poor prognosis (p < 0.001). Conclusions: Our bioinformatics and IHC analyses revealed that BUB1 overexpression was an adverse prognostic factor in LUAD. In vitro experiments demonstrated that BUB1 promoted tumor cell proliferation, migration, and invasion in LUAD. These results indicated that BUB1 was a promising biomarker and potential therapeutic target in LUAD. [ABSTRACT FROM AUTHOR]

ASPP2 is a tumor suppressor that works, at least in part, through enhancing p53-dependent apoptosis. We now describe a new ASPP2 isoform, ΔN-ASPP2, generated from an internal transcription start site that encodes an N-terminally truncated protein missing a predicted 254 amino acids. ΔN-ASPP2 suppresses p53 target gene transactivation, promoter occupancy, and endogenous p53 target gene expression in response to DNA damage. Moreover, ΔN-ASPP2 promotes progression through the cell cycle, as well as resistance to genotoxic stress-induced growth inhibition and apoptosis. Additionally, we found that ΔN-ASPP2 expression is increased in human breast tumors as compared to adjacent normal breast tissue; in contrast, ASPP2 is suppressed in the majority of these breast tumors. Together, our results provide insight into how this new ASPP2 isoform may play a role in regulating the ASPP2-p53 axis. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin, a well-known dietary pigment derived from Curcuma longa, inhibited growth of several types of malignant cells both in vivo and in vitro. Its effects on cell proliferation and the induction of apoptosis in human bladder cancer cell lines and intravesical activity in a rat bladder tumor model were studied. Exposure of human bladder cancer cells to curcumin resulted in the induction of apoptotic cell death and caused cells to arrest in the G2/M phase. The anti-apoptotic Bcl-2 and Survivin protein was downregulated by the curcumin treatment together with enhancement of the Bax and p53 expression. The inhibitory activities of curcumin were stronger than those of cisplatin and could not be prevented by catalase pretreatment in T24 cells. Clonal assay indicated large-dose and short-term curcumin was lethal to bladder cancer cells. Moreover, the in vivo study revealed curcumin did induce apoptosis in situ, inhibit and slow the development of bladder cancer. These observations suggest that curcumin could prove an effective chemopreventive and chemotherapy agent for bladder cancer. [Copyright &y& Elsevier]

The p 53 tumour suppressor gene plays an important role in angiogenesis and apoptosis. The association between Arg72Pro polymorphism and recurrent pregnancy loss (RPL) has been studied but with inconsistent results. A meta-analysis was conducted to examine whether p 53 Arg72Pro polymorphism is a risk factor for RPL. Electronic searchs of PubMed , Embase and Web of Knowledge were conducted to identify relevant studies. The final meta-analysis included six published articles with 730 RPL cases and 613 controls. The pooled results suggested that the variant genotype was associated with the RPL risk in additive model (Pro versus Arg; odds ratio [OR] = 1.28; 95% confidence interval [CI]: 1.06 to 1.54) and recessive model (Pro/Pro versus Arg/Pro + Arg/Arg; OR = 1.82; 95% CI: 1.21 to 2.73). In the stratified analysis by ethnicity, for white people the results were consistent. The Egger's regression asymmetry test suggested a lack of publication bias. Results of this meta-analysis suggest that p 53 codon 72 polymorphism is associated with RPL, especially in white people. Identification of p 53 codon 72 mutation would have some implication for primary prevention of RPL and screening of high-risk individuals. Large well-designed studies are needed to fully describe the association between this polymorphism and RPL. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common malignant tumor in males, which frequently develops into castration-resistant prostate cancer (CRPC). CRPC metastasis is the main reason for its high mortality rate. At present, it lacks effective treatment for patients with CRPC. Raltitrexed (RTX) has been shown to be effective in the treatment of colorectal cancer. However, the effect of RTX on prostate cancer and the underlying mechanism remain unknown. In the current study, we found that RTX could dose-dependently inhibit proliferation, migration, colony formation and induce apoptosis in DU145 and PC-3 cells. RTX also increased ROS generation in prostate cancer cells. Pretreatment with N -acetyl-L-cysteine (NAC) significantly prevented RTX-induced cell apoptosis and endoplasmic reticulum (ER) stress signaling activation in prostate cancer cells. Additionally, we found RTX-induced ROS generation and ER stress activation depended on the expression of heat shock protein family A member 8 (HSPA8). Over-expression of HSPA8 could alleviate RTX-induced cell apoptosis, ROS generation and ER stress signaling activation. Finally, our study also showed that RTX attenuated the tumor growth of prostate cancer in the DU145 xenograft model and significantly downregulated HSPA8 expression and activated ER stress signaling pathway in tumor tissues. Our study is the first to reveal that RTX induces prostate cancer cells apoptosis through inhibiting the expression of HSPA8 and further inducing ROS-mediated ER stress pathway action. This study suggests that RTX may be a novel promising candidate drug for prostate cancer therapy. [Display omitted] • RTX suppressed the cell growth of prostate cancer both in vitro and in vivo. • RTX induced cell apoptosis through increasing ROS generation and activating ER stress signaling in CRPC cells. • RTX induced ROS generation and ER stress activation depended on inhibiting the expression of HSPA8 in CRPC cells. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the expression of miR-155 in plasma and peripheral blood mononuclear cells (PBMCs), the effects of miR-155 on the apoptosis rate of PBMCs and the extent of coronary stenosis in coronary artery disease patients. Seventy chest pain patients were divided into three groups by symptoms, signs, auxiliary examination and coronary arteriography: 21 cases in the acute myocardial infarction group (AMI), 23 cases in the Angor pectoris group (AP) and 26 cases in the control group (CT). The peripheral blood mononuclear cells of the patients in the three groups were separated for cell culture. Annexin V/propidium iodide (PI) was performed to analyze cell apoptosis. RT-qPCR was used to evaluate the expression level of miR-155 in plasma and PBMCs. There were significant differences on the expression of miR-155 in plasma and PBMCs, the apoptosis rate of PBMCs, Gensini score and the extent of coronary stenosis among the three groups (P<0.05). The expression of miR-155 in plasma and PBMCs in AMI and AP group were lower than CT group while the AMI group was lower than the AP group (P<0.05). The apoptotic rate of PBMCs, Gensini score and the extent of coronary stenosis of the AMI and AP groups were higher than CT group while the AMI group was higher than the AP group (P<0.05). The expression of miR-155 in plasma was positively correlated with PBMCs, but negatively correlated with the apoptosis rate of PBMCs, Gensini score and the extent of coronary stenosis. The apoptosis rate of PBMCs in patients with coronary heart disease was positively correlated with the degree of coronary artery stenosis and Gensini score. In conclusion, in the patients with coronary heart disease the apoptosis rate of PBMCs was increased and the expression of miR-155 in plasma and PBMCs cells was decreased, which were correlated with the severity of coronary heart disease. [ABSTRACT FROM AUTHOR]

Highlights: [•] In this study, we found licochalcone B (LCB) could inhibit proliferation of T24 and EJ cells in vitro. [•] S-phase arrest and apoptosis involved in LCB’s antiproliferative effects. [•] Corresponding, we illustrated the possible mechanisms of LCB-induced S-phase arrest and apoptosis. [•] We also demonstrated the antitumor activity of LCB in vivo in MB49 (murine bladder cancer cell line) tumor model. [•] This was the first time to explore the effects of LCB on the bladder cancer cells. [ABSTRACT FROM AUTHOR]

Human CMTM3 has been proposed as a putative tumor suppressor gene. The loss of CMTM3 has been found in several carcinomas. However, the regulation of CMTM3 expression and its function in tumor progression remain largely unknown. Here, we investigated the regulation of CMTM3 expression, function and molecular mechanism in human testicular cancer cells. CMTM3 was frequently downregulated or silenced in testicular cancer cell lines and tumor tissues but highly expressed in normal testis tissues. The re-expression of CMTM3 significantly suppressed the colony formation, proliferation, and migration capacity of testicular cancer cells by inducing a G2 cell cycle arrest and apoptosis. Moreover, the re-expression of CMTM3 activated the transcription of p53, induced p53 accumulation, up-regulated the expression of p21, and increased the cleavage of caspase 9, 8, 3, and PARP. The downregulation of CMTM3 in clinical tumor tissues was associated with the methylation of a single CpG site located within the Sp1/Sp3-responsive region of the core promoter. These results indicate that CMTM3 can function as tumor suppressor through the induction of a G2 cell cycle arrest and apoptosis. CMTM3 is thus involved in testicular cancer pathogenesis, and it is frequently at least partially silenced by the methylation of a single, specific CpG site in tumor tissues. [ABSTRACT FROM AUTHOR]

Abstract: Carbon disulfide (CS2) may lead to spontaneous abortion and very early pregnancy loss in women exposed in the workplace, but the mechanism remains unclear. We designed an animal model in which gestating Kunming strain mice were exposed to CS2 via i.p. on gestational day 4 (GD4). We found that the number of implanted blastocysts on GD8 was significantly reduced by each dose of 0.1 LD50 (157.85mg/kg), 0.2 LD50 (315.7mg/kg) and 0.4 LD50 (631.4mg/kg). In addition, both the level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were increased, showed definite dose–response relationships, and inversely related to the number of implanted blastocysts. The expressions of mRNA and protein for the Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down-regulated. Our results indicated that DNA damage and apoptosis of endometrial cells were important reasons for the loss of implanted blastocysts induced by CS2. [Copyright &y& Elsevier]

Focal adhesion kinase (FAK) is an important therapeutic target in pulmonary artery hypertension (PAH); however, the mechanism of its activation remains unknown. The present study aimed to investigate whether angiotensin-converting enzyme 2 (ACE2) could regulate FAK and alleviate PAH in a rat model of PAH established with a single administration of monocrotaline followed by continuous hypoxia treatment. In the current study, right ventricular pressure, body weight and the right ventricular hypertrophy index were measured, and hematoxylin-eosin staining was performed on lung tissues to determine whether the modeling was successful. Changes in the serum levels of FAK were measured using an ELISA kit to evaluate the association between ACE2 and FAK. The mRNA expression levels of ACE2, FAK, caspase-3 and survivin were determined using reverse transcription-quantitative PCR (RT-qPCR). The protein expression levels of ACE2, phosphorylated FAK/FAK, cleaved caspase-3/pro-caspase-3 and survivin were determined via western blotting. Immunohistochemistry was applied to detect the expression of FAK around the pulmonary arterioles. Apoptosis of smooth muscle cells around pulmonary arterioles was observed by TUNEL staining. After treatment with the ACE2 activator DIZE or inhibitor DX-600, the results demonstrated that ACE2 reduced PAH-induced changes in arteriole morphology compared with the control. It also inhibited FAK expression in serum. WB and RT-qPCR results suggested that ACE2 inhibited the expression of FAK and pathway-related proteins, and promoted caspase-3 expression. Additionally, ACE2 reduced FAK expression around the pulmonary arterioles and promoted smooth muscle cell apoptosis. The results indicated that ACE2 activation inhibited FAK expression, leading to alleviation of the symptoms of PAH. [ABSTRACT FROM AUTHOR]