Neuroglioma is the most common form of human primary malignant brain tumor, more and more studies recently showed only a small subpopulation of glioma cells which called glioma stem cells have true tumorigenic potential. Meanwhile, it was reported the overexpression of JMJD6 protein is closely involvement with the occurrence and development of multiple tumors, and JMJD6 is required for the differentiation of multiple organ, tissues and cells during embryogenesis. However, the influence of JMJD6 overexpression on neuroglioma development is unclear now. Hence, to explore the effects of JMJD6 expression on neuroglioma, we firstly isolated glioma stem cells by using CD133 MicroBead Kit, and identified via neurosphere-forming assay and Immunofluorescence staining. At the same time, we investigated the effects and mechanism of JMJD6 on the proliferation, migration and invasion of glioma stem cells through MTT, transwell assays and the Cignal finder cancer 10-pathway reporter array. The results demonstrated that the glioma neurosphere cells positively expressed stem cell marker SOX2, neuroectodermal stem cell marker Nestin, and also expressed astrocytes marker GFAP and neurons marker β-tubulin III fter FBS-induced differentiation for a week, which proved the glioma neurosphere cells have the self-renewal and multipotential differentiation capacity. Moreover, shRNA lentiviral vector mediated knockdown of JMJD6 in glioma stem cells led to decreased proliferation, migration and invasion, the underlying molecular mechanism is related to the weaken of Wnt signaling pathway and strengthen of p53 signaling pathway.

Non-coding RNAs (ncRNAs) regulate numerous genes and influence the progression of various human diseases, including cancer. The role of regulatory ncRNAs implicated in nasopharyngeal carcinoma (NPC), as well as their target genes, remains unclear. The present study aimed to investigate specific long non-coding (lnc)RNAs, circular RNAs (circRNAs) and mRNAs associated with the molecular pathogenesis of NPC, and to predict the underlying target genes of specific lncRNAs and circRNAs. The expression levels of lncRNAs, circRNAs and mRNAs in NPC and chronic nasopharyngitis tissues were detected and analyzed using microarray and bioinformatics techniques. A total of 2.80% lncRNAs (425 upregulated and 431 downregulated) were significantly differentially expressed (DE) between the two tissue types. Additionally, 0.96% circRNAs (18 upregulated and 13 downregulated) were significantly DE, while 2.94% mRNAs (426 upregulated and 341 downregulated) were significantly DE between the two tissue types. In total, 420 NPC-associated nearby encoding genes (196 up-and 224 downregulated) of the DE lncRNAs were identified. Overlap analysis identified 23 DE circRNAs and their corresponding target genes, with 37 microRNAs and 50 mRNAs, from which 14 interaction networks were constructed. Subsequent pathway analysis revealed 221 DE target genes corresponding to 31 key signaling pathways associated with NPC, 14 of which may represent hub genes associated with NPC pathophysiology. Thus, certain lncRNAs, circRNAs and mRNAs are aberrantly expressed in NPC tissues, and partially specific lncRNAs, circRNAs and their target genes may influence the tumorigenesis and progression of NPC. Target prediction and regulatory network identification may help to determine the pathogenic mechanisms of NPC.

Background: Special AT-rich sequence binding protein 1 (SATB1) is a chromatin organizer and transcriptional regulator which regulate numerous cellular processes through effects on multiple gene expression. SATB1 is associated with drug resistance in several cancers. Whether SATB1 involves radiation resistance in nasopharyngeal carcinoma (NPC) and underlying mechanism of SATB1 to participate in chemoradiotherapy resistance in NPC have not been elaborated. Methods: Chemoradioresistant NPC cell lines 5-8F/DDP (cisplatin) and 5-8F/R (radiation) were developed from 5-8F cell line. The expressions of SATB1, MMP-9 and EMT markers (Vimentin and E-cadherin) in these cell lines were examined by reverse transcription-quantitative (RT-q) PCR and western blot (WB) analysis. Cell viabilities of 5-8F/DDP treated with various concentrations of DDP and 5-8F/R irradiated with various doses of X-ray at the indicated time were investigated by MTT test. SATB1 was silenced in 5-8F/DDP and 5-8F/R cells by short hairpin RNA, and then the expressions of SATB1, MMP-9, Vimentin and E-cadherin were evaluated by RT-qPCR and WB analysis; the abilities of cell proliferation and invasion were assessed using MTT and transwell assays, respectively. Drug and radiation resistance assays were performed after SATB1 knockdown and cell viability was detected by MTT method. Results: SATB1, MMP-9 and Vimentin were markedly upregulated in 5-8F/DDP and 5-8F/R cells compared with 5-8F cell, whereas E-cadherin was obviously downregulated. 5-8F/DDP and 5-8F/R cells displayed drug and radiation resistance to DDP or X-irradiation, respectively, while DDP or X-irradiation inhibited 5-8F cell viability in a time-and dose-dependent manner. Subsequently, knockdown of SATB1 resulted in decreased MMP-9 and Vimentin expression and increased E-cadherin expression in 5-8F/DDP and 5-8F/R. Furthermore, silencing of SATB1 suppressed proliferative and invasive abilities of 5-8F/DDP and 5-8F/R cells. Additionally, SATB1 knockdown reduced drug resistance of 5-8F/DDP cell to DDP and decreased radiation resistance of 5-8F/R cell to X-ray. Conclusion: These results suggest that high expression of SATB1 plays an important role in the malignant behavior of NPC and leads to X-radiation and drug resistance in NPC through promoting EMT process and enhancing MMP-9 expression. SATB1 may be a promising therapeutic target for aggressive and chemoradiation resistant NPC.

In this study, we aimed to precisely define the patterns of allelic loss at the FRA3B site in endemic nasopharyngeal carcinoma and to determine whether an association exists between allelic loss, clinicopathological features and Epstein-Barr virus infection. We examined the loss of heterozygosity in 40 cases of nasopharyngeal carcinoma from an endemic area in southern China, using eight high dense, polymorphic, microsatellite markers within or flanking the FRA3B site. Loss of heterozygosity at the FRA3B region was shown in 31 (77.5 per cent) primary tumours. Loss of heterozygosity was found most frequently at the D3S1300 (55.6 per cent) and D3S2757 (50.0 per cent) loci. The common area of deletion was located between the D3S4103 and D3S4260 loci. In nasopharyngeal carcinoma, loss of heterozygosity at the FRA3B/fragile histidine triad locus correlated with the following clinicopathological parameters: tumour T-stage, lymph node status, clinical stage, tumour differentiation and serum antibody titres of immunoglobulin (Ig) A against Epstein-Barr virus capsid antigen. Significantly frequent loss of heterozygosity was observed in nasopharyngeal carcinoma with tumour stages T3 and T4, lymph node metastasis and advanced tumour-node-metastasis staging (III and IV). Very frequent loss of heterozygosity was also observed to correlate with World Health Organization type III nasopharyngeal carcinoma histopathology. We also found that nasopharyngeal carcinoma patients with high titres of IgA against Epstein-Barr virus capsid antigen showed very frequent loss of heterozygosity. Allelic loss at the FRA3B site occurs significantly more commonly in endemic nasopharyngeal carcinoma patients. This suggests that the region between D3S4103 and D3S4260 may represent a preferential molecular target in nasopharyngeal carcinogenesis.