Zinc-finger protein 382 antagonises CDC25A and ZEB1 signaling pathway in breast cancer.

Our previous studies found that Zinc-finger protein 382 (ZNF382) played as a tumor suppressor gene in esophageal and gastric cancers, and a positive correlation between the high expression of ZNF382 and better outcome in breast cancer patients. However, the biological roles and mechanisms of ZNF382 in breast cancer remains unclear. We detected ZNF382 expression by reverse-transcription PCR (RT-PCR) and real-time quantitative PCR (qRT-PCR) in breast cancer cells and tissues, and explored the impacts and mechanisms of ectopic ZNF382 expression in breast cancer cells in vitro and in vivo, respectively. Our results revealed that ZNF382 was significantly down-regulated in breast cancer tissues compared with adjacent non-cancer tissues. Restoration of ZNF382 expression in silenced breast cancer cells not only inhibited tumor cell colony formation, viability, migration and invasion, and epithelial-mesenchymal-transition (EMT), but also induced apoptosis and G0/G1 arrest. In conclusion, ZNF382 could induce G0/G1 cell cycle arrest through inhibiting CDC25A signaling, and, inhibit cell migration, invasion and EMT by antagonizing ZEB1 signaling in breast cancer cells.

Depression and stress levels increase risk of liver cancer through epigenetic downregulation of hypocretin.

Recent studies suggest that Hypocretin (HCRT, Orexin) are involved in stress regulation of depression through the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanism by which Hypocretin regulate neurobiological responses is unknown. Herein, the effects of chronic stress on the epigenetic modification of HCRT and its association with depression were explored with regard to a potential role in cancer progression. In the study, Sprague Dawley (SD) rats were used to establish an animal model of cancer with depression by administrating n-nitrosodiethylamine (DEN) and chronic unpredictable mild stress (CUMS). RNA-sequencing was used to detect differentially expressed genes in the hippocampus of rats and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of RNA-sequencing. The status of HCRT promoter methylation was assessed by methylation specific polymerase chain reaction. Behavioral tests showed that rats exposed to CUMS had significant depressive-like behaviors. The number of liver tumors and tumor load in depressed rats exposed to CUMS was higher than in SD rats without CUMS. RNA-sequencing revealed that HCRT was one of the most siginificantly downregulated gene in the hippocampus of SD rats with CUMS compared to non-stressed group, which was validated by qRT-PCR. HCRT mRNA expression was downregulated and the promoter for HCRT was hyper-methylated in those with depression. These results identified a critical role for chronic psychological stressors in tumorigenesis and cancer progression, via epigenetic HCRT downregulation. Such epigenetic downregulation may be the molecular basis for the association of cancer with depression.

Transmembrane-4 L-six family member-1 (TM4SF1) promotes non-small cell lung cancer proliferation, invasion and chemo-resistance through regulating the DDR1/Akt/ERK-mTOR axis.

BACKGROUND: Tumor chemo-resistance is a hallmark of malignant tumors as well as the major cause of poor survival rates in lung cancer. Transmembrane-4 L-six family member-1 (TM4SF1), an antigen that serves as an oncogene, mainly affects tumor invasion and metastasis. We investigated the roles of TM4SF1 in non-small-cell lung cancer progression, particularly in the regulation of chemo-sensitivity. METHODS: TM4SF1 was silenced by small interfering RNA transfection.TM4SF1 expression in cell lines and tissues were determined by Quantitative Real-time PCR. MTS, clonogenic, Transwell assay, Flow cytometry verified cell function. By RT-PCR, Western blot, the mechanisms were studied. RESULTS: TM4SF1 was upregulated in both lung cancer cell lines and tissues, compared with 293 T epithelial cells. Analysis of online databases revealed that high expression of TM4SF1 is associated with the older patient age, smoking habits, and poor patient survival and outcome. Knockdown of TM4SF1 substantially inhibited tumor cell growth, migration, and invasion, and enhanced the chemo-sensitivity of the lung cancer cell lines A549 and H1299 to cisplatin and paclitaxel. Furthermore, the silencing of TM4SF1 induced lung cancer cell apoptosis and arrested cells at the G2/M phase. These results suggest that TM4SF1 is associated with lung cancer progression and appears to be required for tumor cell growth, maintenance of chemo-resistance and metastasis. We further found that TM4SF1 exerts these effects in part by regulating the expression of the discoidin domain receptor DDR1 and its downstream target, the Akt/ERK/mTOR pathway, and consequently alters cell sensitivity to chemo-reagents and contributes to invasion and metastasis. CONCLUSIONS: These findings demonstrate that TM4SF1 may serve as a prognostic factor for lung cancer chemo-response and patient outcome.

Risk Factors for Post-Acute Coronary Syndrome Depression: A Meta-analysis of Observational Studies.

BACKGROUND: The incidence of depression is very common among patients with post-acute coronary syndrome (ACS) and leads to adverse outcomes. AIMS: The aim of this meta-analysis was to detect risk factors for depression among patients with ACS and to provide clinical evidence for its prevention. METHODS: The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline to search the PubMed, Web of Science, EMBASE, and EBSCO databases from January 1996 to March 2018. Data that met the inclusion criteria were extracted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk factors of post-ACS depression. RESULTS: A total of 30 articles met the inclusion criteria, and 25 risk factors were found to be associated with depression. The top 5 risk factors are as follows: antidepression treatment (OR, 4.25; 95% CI, 3.41-5.31), housewife status (OR, 4.17; 95% CI, 1.83-9.53), history of depressive disorders (OR, 3.52; 95% CI, 2.69-4.61), widow status (OR, 2.34; 95% CI, 1.05-5.21), and history of congestive heart failure (OR, 2.03; 95% CI, 1.04-3.97). The authors also found that a married status, high education level, and employment are protective factors. CONCLUSION: Clinical personnel should be alerted with regard to the high risk factors of depression, including female gender, low education level, unmarried status, living alone, unemployed status, unhealthy lifestyle, and complications such as cardiovascular, respiratory, and metabolic diseases. In particular, staff should pay attention to a history of previous depression, be concerned with the psychological condition of the patient, and monitor and perform early interventions to reduce the incidence of depression.