LncRNA GAS5 plays a tumor suppressive role in a variety of human cancers and promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. However, the role of GAS5 in nasopharyngeal carcinoma (NPC) remains elusive. The objective of the present study was to evaluate the effect of single nucleotide polymorphisms (SNPs) in GAS5 on treatment efficacy and toxicity in NPC patients receiving chemoradiotherapy. Three potentially functional SNPs of GAS5 were genotyped in 267 NPC patients and validated in another 238 NPC patients treated with chemoradiotherapy from southern China. Multivariate logistic regression analyses and stratification analyses were used to estimate the association of candidate SNPs and chemoradiotherapy efficacy and toxic reactions. Our results showed that rs2067079 kept a consistent association with severe myelosuppression and severe neutropenia in discovery set (OR=2.403, P=0.009; OR=2.454, P=0.015; respectively), validation set (OR=3.653, P=0.027; OR=4.767, P=0.016; respectively), and combined dataset (OR=1.880, P=0.007; OR=2.079, P=0.005; respectively). rs2067079 CT genotype carriers presented an even more remarkable increased risk of severe myelosuppression (OR=3.878, P=0.003) and severe neutropenia (OR=3.794, P=0.009) in subgroups taking paclitaxel+platinum as concurrent chemoradiotherapy regimen. Besides, we found a gene-does effect of rs6790, with the incidence rate of severe myelosuppression decreased from 23.56% to 17.21% to 10% and the incidence rate of severe neutropenia decreased from 30.4% to 20.9% to 17.1% for rs6790 GG vs GA vs AA genotype carriers. Our results indicate the potential role of lncRNA GAS5 polymorphisms rs2067079 and rs6790 as predictive biomarkers for chemoradiotherapy induced toxic reactions in NPC patients.

Colon cancer stem cell (cCSC) is considered as the seed cell of colon cancer initiation and metastasis. Cyclooxygenase-2 (COX2), a downstream target of NFκB, is found to be essential in promoting cancer stem cell renewal. However, how COX2 is dysregulated in cCSCs is largely unknown. In this study, we found that the expression of transcription factor FOXP3 was much lower in the spheroids than that in the parental tumor cells. Overexpression of FOXP3 significantly decreased the numbers of spheres, reduced the side population. Accordingly, FOXP3 expression decreased the tumor size and weight in the xenograft model. The tumor inhibitory effects of FOXP3 were rarely seen when COX2 was additionally knocked down. Mechanically, FOXP3 transcriptionally repressed COX2 expression via interacting with and thus inhibiting p65 activity on the putative NFκB response elements in COX2 promoter. Taken together, we here revealed possible involvement of FOXP3 in regulating cCSC self-renewal via tuning COX2 expression, and thus providing a new target for the eradication of colon cancer stem cells.