Background/Aims: Programmed death ligand1(PD-L1) plays a role in the development and progression of non-small cell lung cancer (NSCLC). This study aimed to identify miRNA(s) that are responsible for regulation of expression of PD-L1 in NSCLC, and to investigate the role of PD-L1 in regulation of the cell cycle in NSCLC. Methods: We predicted the target miRNA of PD-L1, which was miR-140, using the online tools TargetScan and miBase. In NSCLC cells obtained from clinical specimens, in addition to A549 and NCI-H1650 cell cultures, western blots were used to detect the level of expression of proteins, while real-time PCR was used to determine the level of expression of PD-L1, miR-140, cyclin E, and β-actin. Transfection with miR-140 mimics, miR-140 inhibitors, and PD-L1 siRNA were conducted using commercial kits. To determine whether miR-140 directly binds PD-L1, a luciferase reporter gene with wild type or mutated PD-L1 was used. Cell viability was measured with the MTT assay, and PI staining was used for cell cycle analysis. Results: We found low expression of miR-140 and high expression of PD-L1 and cyclin E in NSCLC cells. Over-expression of miR-140 suppressed the expression of PD-L1 by directly binding its 3’ UTR, and was also associated with decreased expression of cyclin E and inhibition of cellular proliferation in A549 and NCI-H1650 cells. Inhibition of PD-L1, in the absence of manipulations to miR-140, also decreased the expression of cyclin E. Conclusion: We conclude that miR-140 directly suppresses PD-L1 and inhibits the miR-140/PD-L1/cyclin E pathway in NSCLC.

Genetic variations in the xeroderma pigmentosum group D (XPD) gene may increase cancer susceptibility by affecting the capacity for DNA repair. A lot of studies have reported the association of XPD Lys751Gln polymorphism with risk of cancer, but the results remained controversial. Hence, we performed a systematic review and conducted a meta-analysis to explore association of the XPD Lys751Gln polymorphism with risk of cancer (78,398 cases and 103,178 controls from 224 studies). Overall, a significantly increased cancer risk was found in all genetic models (dominant model: odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.06-1.14; recessive model: OR = 1.10, 95% CI = 1.05-1.15; homozygous model: OR = 1.14, 95% CI = 1.08-1.21; heterozygous model: OR = 1.09, 95% CI = 1.05-1.12; additive model: OR = 1.08, 95% CI= 1.05-1.11) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk of cancer remained for subgroups of breast cancer, esophageal cancer, hepatocellular cancer, leukemia, lung cancer, and melanoma. In summary, this meta-analysis suggests the XPD Lys751Gln polymorphism is a genetic susceptibility for some cancer types. Moreover, ethnicity, histological type of cancer, and smokers seem to contribute to varying expressions of the Lys751Gln on some cancer risk. In addition, our work also points out the importance of new studies for Lys751Gln association in endometrial cancer and ovarian cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the Lys751Gln polymorphism in cancer development.

BackgroundWhile the association between physical activity (PA) and depression has been established, there is limited research on the effect of PA on the risk of depression among Chinese individuals. Thus, this study aimed to investigate the relationship between PA and depression among Chinese individuals.MethodsWe used a stratified random sampling approach to recruit participants from five urban districts in Wuhan, China. A total of 5,583 permanent residents aged 18 years or older completed questionnaires, which included the International Physical Activity Questionnaire Short Form (IPAQ-SF) to measure PA, and the 9-item Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. To control for potential confounders, multiple logistic regression was employed to assess the association of PA with depression.ResultsThe depression group had significantly lower weekly PA levels, measured in metabolic equivalent of task-minutes per week (MET-min/w), compared to the non-depression group [1,770 (693–4,200) MET-min/w vs. 2,772 (1,324–4,893) MET-min/w, p < 0.001]. In the fully adjusted model, the moderate and high PA level groups had lower odds ratios (ORs) for depressive symptoms compared to the low PA level group [OR (95% confidence interval (CI)) = 0.670 (0.523–0.858), 0.618 (0.484–0.790), respectively]. Among males, moderate and high levels of PA were associated with lower risk of depression compared to low PA levels [OR (95% CI) = 0.417 (0.268–0.649), 0.381 (0.244–0.593), respectively]. However, this association was not observed in females [OR (95% CI) = 0.827 (0.610–1.121), 0.782 (0.579–1.056), respectively]. The study found a significant interaction between PA levels and gender in relation to depression (P for interaction = 0.019).ConclusionThe findings suggest a negative association between PA and risk of depressive symptoms, indicating that moderate to high levels of PA may serve as a protective factor against depressive symptoms.