Background: Monocarboxylate transporter isoform 1 (MCT1) is an important molecule in mediating lactate transportation. Recent studies have shown an oncogenic role of MCT1 in cancer development.Methods: In this study, we aimed to investigate the expression and role of MCT1 in bladder cancer (BCa). MCT1 expression was detected in 124 BCa tissues and their clinicopathological significance was analyzed. We also used The Cancer Genome Atlas database to explore the prognostic association of MCT1 with BCa. Cell proliferation, migration and invasion assays were performed on BCa cells in which MCT1 was downregulated. The effect of MCT1 on BCa cell aerobic glycolysis, as well as its association with HIF-1α, was tested.Results: We found that high MCT1 expression correlated with lymph node and distant metastasis. Patients with high-MCT1 expression showed shorter overall survival than those with low-MCT1 expression. Knockdown of MCT1 inhibited BCa cell proliferation, migration and invasion, and affected expression of epithelial-mesenchymal transition related proteins. Downregulation of MCT1 decreased lactate levels in cell medium, as well as HK2, GLUT1 and LDHB expression. In addition, MCT1 expression was partly dependent on HIF-1α.Conclusions: Taken together, our study has shown a prognostic role of MCT1 in BCa, and provided potential diagnostic and therapeutic options for BCa patients.
Matrix metalloproteinase-2 (MMP-2) has been shown to play a pivotal role in the pathophysiology of lumbar disc disease (LDD). Increased expression and activity of MMP-2 has been documented in degenerative discs. The polymorphism -1306C/T in the promoter region of MMP-2 gene was reported to influence gene transcription and expression. The objective of this study was therefore to investigate the possible association of MMP-2 -1306C/T polymorphism with the occurrence and the clinical characteristics of LDD. MMP-2 genotypes were determined by polymerase chain reaction (PCR) and direct DNA sequencing in a case-control study involving 162 younger patients with LDD and 318 age-and sex-matched healthy adults. The results showed that the frequency of MMP-2 -1306CC genotype was significantly higher in LDD patients when compared with controls. Subjects with the CC genotype had nearly threefold increased risk for LDD (odds ratio 3.08; 95% confidence interval 1.84-5.16) compared with subjects carrying at least one variant T allele. Furthermore, this genotype was found to correlate with more severe grades of disc degeneration observed on magnetic resonance imaging scan. These findings suggest that MMP-2 -1306C/T polymorphism may be a genetic risk factor related to LDD susceptibility in the young adult population.
Objectives To identify the association between night shift work and the risk of various cancers with a comprehensive perspective and to explore sex differences in this association. Methods We searched PubMed, Embase, and Web of Science for studies on the effect of night shift work on cancer, including case-control, cohort, and nested case-control studies. We computed risk estimates with 95% confidence intervals (CIs) in a random or fixed effects model and quantified heterogeneity using the I
2 statistic. Subgroup, metaregression, and sensitivity analyses were performed to explore potential sources of heterogeneity. Contour-enhanced funnel plots and the trim and fill method were used together to analyze bias. Linear dose–response analysis was used to quantitatively estimate the accumulative effect of night shift work on the risk of cancer. Results Fifty-eight studies were eligible for our meta-analysis, including 5,143,838 participants. In the random effects model, the pooled odds ratio (OR) of cancers was 1.15 (95% CI = 1.08–1.22, P < 0.001; I
2 = 76.2%). Night shift work increased the cancer risk in both men (OR = 1.14, 95% CI = 1.05–1.25, P = 0.003) and women (OR = 1.12, 95% CI = 1.04–1.20, P = 0.002). Subgroup analyses showed that night shift work positively increased the risk of breast (OR = 1.22, 95% CI = 1.08–1.38), prostate (OR = 1.26, 95% CI = 1.05–1.52), and digestive system (OR = 1.15, 95% CI = 1.01–1.32) cancers. For every 5 years of night shift work, the cancer risk increased by 3.2% (OR = 1.032, 95% CI = 1.013–1.051). Conclusion This is the first meta-analysis identifying the positive association between night shift work and the risk of cancer and verifying that there is no sex difference in the effect of night shift work on cancer risk. Cancer risk increases with cumulative years of night shift work.
Recent studies have indicated that low circulating adiponectin concentrations are associated with a higher risk of several cancers, including renal cell carcinoma. In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell renal cell carcinoma (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The association of serum adiponectin concentration with genetic variants was calculated using a multivariate linear regression model. A significantly higher ccRCC risk was associated with the rs182052 variant A allele (adjusted OR, 1.36 and 95% CI, 1.07–1.74 for AA vs GG, P = 0.013; adjusted OR, 1.27 and 95% CI, 1.04–1.56 for AA vs GG+AG, P = 0.019), and this positive association was more evident in overweight subjects. Fasting serum adiponectin was lower in subjects carrying A alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell RCC (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Fasting serum adiponectin was lower in subjects carrying minor alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.
MicroRNAs (miRNAs) are involved in cancer development and progression. Renal cell carcinoma (RCC) frequently undergoes metastasis and has a high mortality rate. The current study measured miRNA-126 (miR-126) expression levels in 128 pairs of clear cell RCC and adjacent normal kidney tissue samples by reverse transcription-quantitative polymerase chain reaction, and analyzed the association between miR-126 and various clinicopathological parameters. In addition, cell proliferation, wound healing and cell invasion assays were conducted using RCC cells overexpressing miR-126. Potential miR-126 target genes and the signaling pathways that may be regulated by miR-126 were then examined. miR-126 expression was significantly reduced in patients with metastatic RCC compared with patients without metastasis. Consistently, overexpression of miR-126 in RCC cells significantly inhibited cell proliferation, migration and invasion in vitro compared with negative control miRNA. A luciferase reporter assay demonstrated that miR-126 targets Rho associated coiled-coil containing protein kinase 1 (ROCK1) by directly binding the 3′-untranslated region. Furthermore, western blotting identified miR-126 as an important regulator of the AKT and extracellular signal-regulated 1/2 signaling pathways. The results of the present study indicate that miR-126 inhibits RCC cell proliferation, migration and invasion by downregulating ROCK1. These findings suggest that miR-126 may be valuable as a potential target for therapeutic intervention in RCC.
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