Machine learning immune-related gene based on KLRB1 model for predicting the prognosis and immune cell infiltration of breast cancer.

Objective: Breast cancer is a prevalent malignancy that predominantly affects women. The development and progression of this disease are strongly influenced by the tumor microenvironment and immune infiltration. Therefore, investigating immune-related genes associated with breast cancer prognosis is a crucial approach to enhance the diagnosis and treatment of breast cancer. Methods: We analyzed data from the TCGA database to determine the proportion of invasive immune cells, immune components, and matrix components in breast cancer patients. Using this data, we constructed a risk prediction model to predict breast cancer prognosis and evaluated the correlation between KLRB1 expression and clinicopathological features and immune invasion. Additionally, we investigated the role of KLRB1 in breast cancer using various experimental techniques including real-time quantitative PCR, MTT assays, Transwell assays, Wound healing assays, EdU assays, and flow cytometry. Results: The functional enrichment analysis of immune and stromal components in breast cancer revealed that T cell activation, differentiation, and regulation, as well as lymphocyte differentiation and regulation, play critical roles in determining the status of the tumor microenvironment. These DEGs are therefore considered key factors affecting TME status. Additionally, immune-related gene risk models were constructed and found to be effective predictors of breast cancer prognosis. Further analysis through KM survival analysis and univariate and multivariate Cox regression analysis demonstrated that KLRB1 is an independent prognostic factor for breast cancer. KLRB1 is closely associated with immunoinfiltrating cells. Finally, in vitro experiments confirmed that overexpression of KLRB1 inhibits breast cancer cell proliferation, migration, invasion, and DNA replication ability. KLRB1 was also found to inhibit the proliferation of breast cancer cells by blocking cell division in the G1/M phase. Conclusion: KLRB1 may be a potential prognostic marker and therapeutic target associated with the microenzymic environment of breast cancer tumors, providing a new direction for breast cancer treatment.

Erratum: Long non-coding RNA BX357664 inhibits cell proliferation and metastasis in human lung cancer.

[This corrects the article DOI: 10.3892/ol.2019.9886.].

Magnesium reduces cadmium accumulation by decreasing the nitrate reductase-mediated nitric oxide production in Panax notoginseng roots.

Panax notoginseng is a traditional medicinal herb in China. However, the high capacity of its roots to accumulate cadmium (Cd) poses a potential risk to human health. Our previous study showed that nitrate reductase (NR)-dependent nitric oxide (NO) production promoted Cd accumulation in P. notoginseng root cell walls. In this study, the role of Mg in the regulation of NO production and Cd accumulation in P. notoginseng roots was characterized. Exposure of P. notoginseng roots to increasing concentrations of Cd resulted in a linear increase in NO production. The application of 2 mM Mg for 24 h significantly alleviated Cd-induced NO production and Cd accumulation in roots, which coincided with a significant decrease in the NR activity. Western analysis suggested that Mg increased the interaction between the 14-3-3 protein and NR, which might have been a reason for the Mg-mediated decrease in NR activity and NO production under Cd stress. These results suggested that Mg-mediated alleviation of Cd-induced NO production and Cd accumulation is achieved by enhancement of the interaction between the 14-3-3 protein and NR in P. notoginseng roots.

Long non-coding RNA BX357664 inhibits cell proliferation and metastasis in human lung cancer.

Long non-coding RNAs (lncRNAs) have been investigated in human carcinogenesis. The lncRNA BX357664 has emerged as a novel lncRNA that was initially recognized by a microarray analysis. The present study aimed to identify the expression and functional roles of lncRNA BX357664 in lung cancer. The transcription level of BX357664 was initially revealed to be downregulated in clinical lung cancer tissues and in a series of lung cancer cell lines. Clinical data demonstrated that the high expression of BX357664 was associated with tumor size, distant metastasis and Tumor-Node-Metastasis stage. Following the overexpression of BX357664 in A549 and 95D cells, the potential of cells to form colonies, as well as the proliferation and motility abilities, were revealed to be decreased. Furthermore, the cell cycle was arrested in the G0/G1 phase by BX357664 modulation. Transwell analysis and a wound-healing assay also demonstrated that overexpression of BX357664 in A549 and 95D cells significantly inhibited cell migration and invasion. These data suggested that BX357664 inhibits cell proliferation and metastasis in lung cancer. The results of the present study provided evidence that BX357664 is a novel lncRNA that may aid in the diagnosis and treatment of lung cancer.

MicroRNAs as noninvasive biomarkers in bladder cancer detection: a diagnostic meta-analysis based on qRT-PCR data.

OBJECTIVE: As the diagnostic significance of microRNAs (miRNAs) in the detection of bladder cancer is controversial, we aimed to perform a meta-analysis to comprehensively assess the diagnostic value of miRNAs in blood and urine for detecting bladder cancer. METHODS: A systematic literature search of public databases was conducted to obtain qualified studies. Sensitivity was utilized to plot the summary receiver operator characteristic (SROC) curve against specificity and the area under the SROC curve (AUC) was generated to evaluate the pooled diagnostic efficiency. Subgroup analyses and meta-regression were applied to investigate the underlying sources of heterogeneity. The STATA 12.0 software was used to perform all statistic analyses. RESULTS: A total of 58 studies from 22 articles comprising 4,558 bladder cancer patients and 4,456 controls were included in our meta-analysis. MiRNAs in blood and urine manifested relatively good diagnostic efficiency in detecting bladder cancer, with a sensitivity of 0.74, a specificity of 0.78, and an AUC of 0.83. Multiple-miRNA assays were more accurate than single-miRNA ones in bladder cancer diagnosis. Blood-based miRNA assays displayed better diagnostic performance than urine-based ones. In addition, miRNAs showed reduced diagnostic value in bladder cancer among Caucasians compared with Asians. CONCLUSIONS: MiRNAs in blood and urine, especially the combination of multiple miRNAs, may serve as hopeful noninvasive biomarkers for early diagnosis of bladder cancer. Further extensive prospective research is needed to verify their clinical significance in bladder cancer diagnosis.

Association of tagging SNPs in the MTHFR gene with risk of type 2 diabetes mellitus and serum homocysteine levels in a Chinese population.

Diabetes is a global public health crisis, and the prevalence is increasing rapidly. Folate supplementation is proved to be effective in reducing the risk of diabetes or improving its symptoms. Methylenetetrahydrofolate reductase is an important enzyme involved in folate metabolism. The aim of this study is to examine whether polymorphisms in the MTHFR gene are associated with risk of type 2 diabetes mellitus (T2DM) and fasting total serum homocysteine (tHcy) levels. We genotyped nine tagging SNPs in the MTHFR gene in a case-control study, including 595 T2DM cases and 681 healthy controls in China. We found that C allele of rs9651118 had significant decreased risk of T2DM (adjusted odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.55-0.87, P = 0.002) compared with T allele. Haplotype analysis also showed that MTHFR CTCCGA haplotype (rs12121543-rs13306553-rs9651118-rs1801133-rs2274976-rs1801131) had significant reduced risk of T2DM (adjusted OR = 0.71, 95% CI: 0.58-0.87, P = 0.001) compared with CTTTGA haplotype. Besides, the MTHFR rs1801133 was significantly associated with serum levels of tHcy in healthy controls (P = 0.0002). These associations were still significant after Bonferroni corrections (P < 0.0056). These findings suggest that variants in the MTHFR gene may influence the risk of T2DM and tHcy levels.