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BackgroundAberrant activation of the proto-oncogene B-cell lymphoma/leukemia 11A (BCL11A) has been implicated in the pathogenesis of leukemia and lymphoma. However, the clinical significance of BCL11A in non-small cell lung cancer (NSCLC) remains unknown.ResultsWe examined BCL11A expression at the protein and mRNA levels in a cohort (n = 114) of NSCLC patients and assessed the relationship between BCL11A expression and clinicopathological parameters. Data from array-based Comparative Genomic Hybridization (aCGH) and microRNA transfection experiments were integrated to explore the potential mechanisms of abnormal BCL11A activation in NSCLC. Compared to adjacent non-cancerous lung tissues, BCL11A expression levels were specifically upregulated in NSCLC tissues at both the mRNA (t = 9.81, P < 0.001) and protein levels. BCL11A protein levels were higher in patients with squamous histology (χ2 = 15.81, P = 0.001), smokers (χ2 = 8.92, P = 0.004), patients with no lymph node involvement (χ2 = 5.14, P = 0.029), and patients with early stage disease (χ2 = 3.91, P = 0.048). A multivariate analysis demonstrated that in early stage NSCLC (IA–IIB), BCL11A was not only an independent prognostic factor for disease-free survival (hazards ratio [HR] 0.24, 95% confidence interval [CI] 0.12-0.50, P < 0.001), but also for overall survival (HR = 0.23, 95% CI 0.09-0.61, P = 0.003). The average BCL11A expression level was much higher in SCC samples with amplifications than in those without amplifications (t = 3.30, P = 0.023). Assessing functionality via an in vitro luciferase reporter system and western blotting, we found that the BCL11A protein was a target of miR-30a.ConclusionsOur results demonstrated that proto-oncogene BCL11A activation induced by miR-30a and gene amplification may be a potential diagnostic and prognostic biomarker for effective management of this disease.

Carvacrol, a component of thyme oil, as a novel antitumor agent, has been implicated in several types of cancer cells. However, the mechanisms underlying the effect of carvacrol in human oral squamous cell carcinoma (OSCC) remain unclear. Here, we report that carvacrol significantly inhibits tumor cell proliferation, metastasis and invasion, and induces apoptosis in OSCC. Our results demonstrated that the molecular mechanisms of the effect of carvacrol in Tca-8113 induces G1/S cell cycle arrest through downregulation of CDK regulator CCND1 and CDK4, and upregulation of CDK inhibitor P21. Further analysis demonstrated that carvacrol also inhibited Tca-8113 cells’ clone formation in clonogenic cell survival assay. Student’s t-test (two-tailed) was used to compare differences between groups, and the significance level was P<0.01. Then, treatment of Tca-8113 cells with carvacrol resulted in downregulation of Bcl-2, Cox2, and upregulation of Bax. Carvacrol significantly inhibited the migration and invasion of human OSCC cells by blocking the phosphorylation of FAK and MMP-9 and MMP-2, transcription factor ZEB1, and β-catenin proteins’ expression. Taken together, these results provide novel insights into the mechanism of carvacrol and suggest potential therapeutic strategies for human OSCC.

Objective: Cyclooxygenase (COX)-2, an inducible isoform of the major rate-limiting enzymes that regulate the production of prostaglandins is associated with injury, inflammation and proliferation. We sought to examine whether plasma COX-2 levels and its genetic variants is associated with salt sensitivity, BP changes and/or hypertension in humans. Methods: Eighty participants (aged 18–65 years) were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families from seven Chinese villages in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension. Results: Plasma COX-2 levels were significantly decreased with reduction of salt intake from the usual to a low-salt diet and decreased further when converting from the low-salt to the high-salt diet. SNPs rs12042763 in the COX-2 gene was significantly associated with SBP responses to both low-salt and high-salt diet. SNPs rs689466 and rs12042763 were significantly associated with longitudinal changes in BPs. In addition, several COX-2 SNPs were significantly associated with incident hypertension over an 8-year follow-up. Gene-based analyses also supported the overall association of COX-2 with longitudinal changes in SBP and hypertension incidence. Conclusion: This study shows that dietary salt intake affects plasma COX-2 levels and that COX-2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations studied.

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