Zinc finger protein 468 up-regulation of TFAM contributes to the malignant growth and cisplatin resistance of breast cancer cells.

BACKGROUND: Because of the progress on the diagnosis and treatment for patients with breast cancer (BC), the overall survival of the patients has been improved. However, a number of BC patients cannot benefit from the existing therapeutic strategies as the essential molecular events triggering the development of BC are not well understood. Previous studies have shown that abnormal expression of zinc finger proteins is involved in the development of various malignancies, whereas it remains largely unclear on their significance during the progression of BC. In this study, we aimed to explore the clinical relevance, cellular function and underlying mechanisms of zinc finger protein 468 (ZNF468) in BC. METHODS: The clinical relevance of ZNF468 and TFAM was analyzed based on TCGA database. Overexpression or knockdown of ZNF468 and TFAM were performed by transfecting the cells with overexpression plasmids and siRNAs, respectively. Overexpression and knockdown efficacy was checked by immunoblotting. CCK-8, colony formation, transwell and apoptosis experiments were conducted to check the cellular function of ZNF468 and TFAM. The content of mtDNA was measured by the indicated assay kit. The effects of cisplatin on BC cells were detected by CCK-8 and colony formation assays. The regulation of ZNF468 on TFAM was analyzed by RT-qPCR, immunoblotting, dual luciferase activity and ChIP-qPCR assays. RESULTS: ZNF468 was overexpressed in BC patients and inversely correlated with their prognosis. Based on overexpression and knockdown assays, we found that ectopic expression of ZNF468 was essential for the proliferation, growth and migration of BC cells. The expression of ZNF468 also negatively regulated the sensitivity of BC cells to the treatment of cisplatin. Mechanistically, ZNF468 potentiated the transcription activity of TFAM gene via direct binding on its promoter. Lastly, we demonstrated that ZNF468 up-regulation of TFAM was important for the growth, migration and cisplatin resistance in BC cells. CONCLUSION: Our study indicates that ZNF468 promotes BC cell growth and migration via transcriptional activation of TFAM. ZNF468/TFAM axis can serve as the diagnostic and therapeutic target, as well as the predictor of cisplatin effectiveness in BC patients.

Cyclin B1 expression as an independent prognostic factor for lung adenocarcinoma and its potential pathways.

Although great progress has been made in the early diagnosis and targeted therapy of lung adenocarcinoma (LUAD), the survival of patients with LUAD remains unsatisfactory. There is an urgent requirement for new biomarkers to guide the diagnosis, prognosis and treatment of LUAD. Following an initial bioinformatics screen, the present study focused on cyclin B1 (CCNB1) in LUAD. A total of 94 patients with LUAD from a single hospital were included in the study. CCNB1 protein expression was detected and scored in 94 LUAD samples and 30 normal tissue samples by immunohistochemistry. The associations between CCNB1 expression and the clinicopathological features of the patients with LUAD were analyzed. Furthermore, the relationship between prognosis and the CCNB1 expression level was analyzed using Cox regression and survival analyses. Weighted gene co-expression network analysis and RNA-sequencing were also applied to identify the potential molecular mechanisms of CCNB1 in LUAD. CCNB1 was highly expressed in patients with LUAD and was associated with poor prognosis. It may affect the expression of CPLX1, PPIF, SRPK2, KRT8, SLC20A1 and CBX2 genes and function via different pathways. CCNB1 has the potential to become a novel prognostic target for LUAD.

Association between lncRNA H19 rs217727 polymorphism and the risk of cancer: an updated meta-analysis.

BACKGROUND: We have performed this study to evaluate the association between H19 rs217727 polymorphism and the risk of cancer. METHODS: An odds ratio (OR) with a 95% confidence interval (CI) was applied to determine a potential association. RESULTS: A total of 17 case-control publications were selected. This meta-analysis showed that H19 rs217727 has a significant increased association with cancer risk in allelic, homozygous, heterozygote, dominant and recessive models (T vs C: OR = 1.16, 95% CI = 1.06-1.27, I2 = 75.7; TT vs CC: OR = 1.29, 95% CI = 1.06-1.56, I2 = 71.6; CT vs CC: OR = 1.15, 95% CI = 1.01-1.31, I2 = 75.4; CT + TT vs CC: OR = 1.20, 95% CI = 1.05-1.36, I2 = 76.5; TT vs CT + CC: OR = 1.22, 95% CI = 1.02-1.45, I2 = 70.6;). In the subgroup analysis of smoking status, both smokers and nonsmokers showed an increase in cancer risk in allelic, homozygous, dominant and heterozygote models. CONCLUSION: This meta-analysis revealed H19 rs217727 may influence cancer susceptibility.

Network Pharmacology Integrated Molecular Docking Reveals the Antiosteosarcoma Mechanism of Biochanin A.

BACKGROUND: As the malignant tumor with the highest incidence in teenagers, osteosarcoma has become a major problem in oncology research. In addition to surgical management, the pharmacotherapeutic strategy for osteosarcoma treatment is an attractive way to explore. It has been demonstrated that biochanin A has an antitumor capacity on multiple kinds of solid tumor, including osteosarcoma. But the precise mechanism of biochanin A against osteosarcoma is still needed to be discovered. OBJECTIVE: To identify the potential therapeutic targets of biochanin A in treating osteosarcoma. METHODS: In present study, an integrated approach including network pharmacology and molecular docking technique was conducted, which mainly comprises target prediction, network construction, gene ontology, and pathway enrichment. CCK8 test was employed to evaluate the cell viability of MG63 cells. Western-blot was used to verify the target proteins of biochanin A. RESULTS: Ninety-six and 114 proteins were obtained as the targets of biochanin A and osteosarcoma, respectively. TP53, IGF1, JUN, BGLAP, ATM, MAPK1, ATF3, H2AFX, BAX, CDKN2A, and EGF were identified as the potential targets of biochanin A against osteosarcoma. Based on the western-blot detection, the expression of BGLAP, BAX, and ATF3 in MG63 cell line changed under the treatment of biochanin A. CONCLUSION: Biochanin A can effectively suppress the proliferation of osteosarcoma and regulate the expression of BGLAP, BAX, and ATF3, which may act as the potential therapeutic targets of osteosarcoma.

Clinicopathological and prognostic significance of zinc finger antisense 1 overexpression in cancers: A meta-analysis.

BACKGROUND: An increasing number of studies have recently highlighted the role of zinc finger antisense 1(ZFAS1) as a prognostic marker in cancers. However, these results remain controversial. Hence, a meta-analysis was conducted to further investigate the effects of ZFAS1 expression on clinicopathological features and survival outcomes. METHOD: All eligible studies were searched from PubMed, Embase, Web of Science, and the Cochrane Library. All included articles evaluated the relationship between the expression levels of ZFAS1 and survival, or the range of pathological features in cancer patients. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to evaluate the effect of ZFAS1 expression on overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS). The relationship between ZFAS1 expression and clinicopathological features was determined through pooled odds ratios (ORs) and 95% CIs. RESULTS: In total 8 studies, which comprised of 820 patients, were qualified for analysis. Results revealed that the overexpression of ZFAS1 was significantly associated with poor OS (HR = 1.97, 95% CI: 1.53-2.54), worse RFS (HR = 1.95, 95% CI: 1.24-3.04) and worse DFS (HR = 2.35, 95% CI: 1.43-3.88) in cancers. Further subgroup analysis revealed that ZFAS1 overexpression was significantly correlated with poor OS in different cancer types, HR obtain methods and sample sizes. In addition, this meta-analysis revealed that the upregulated expression of ZFAS1 was significantly associated with lymph node metastasis, Tumor Node Metastasis (TNM) stage, and tumor size. CONCLUSIONS: This meta-analysis revealed that the expression of ZFAS1 was associated with tumor prognosis. ZFAS1 could be used as a predictor for tumor progression in various cancers.