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Nasopharyngeal carcinoma (NPC) is the most common nasopharyngeal squamous cell carcinoma, and recurrence and metastasis are still difficult problems in its current treatment. This study aimed to investigate the effect of SUMO modification of STAT1 protein on the proliferation and invasion of NPC, and to reveal the underlying mechanism. Two gene expression profiles (GSE12452 and GSE53819) of 49 nasopharyngeal carcinomas and 28 normal controls were analyzed to identify differentially expressed genes. In total, 448 up-regulated genes and 622 down-regulated genes were identified. In addition, 16 SUMO-related molecules in the NPC dataset GSE102349 with survival data were analyzed, and it was found that the high expression of SENP1 and SENP2 was closely related to the poor prognosis of NPC. GO and GSEA analysis suggested that immune-related biological processes, IFN-γ-STAT signaling pathway and protein modification-related molecules were significantly enriched in NPC, resulting in poor survival prognosis. In order to verify the results of bioinformatics analysis and explore its underlying molecular mechanisms, western blot, Immunofluorescence, Immunoprecipitation and Immunohistochemistry are conducted in NPC cells, animals and clinical samples. SENP1 and STAT protein levels were increased in NPC tissues. SENP1 inhibited SUMOylation of STAT1, thereby promoting the protein level of STAT1 and the nuclear translocation. SENP1 promoted the proliferation and invasion of NPC by inducing STAT1. Overall, SENP1-induced deSUMOylation of STAT1, resulting in an increased proliferation and invasion of nasopharyngeal carcinoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Nasopharyngeal carcinoma (NPC) is an epithelial cancer emerging from the lining of nasopharyngeal mucosa, with extremely frequent occurrence in east and southeast Asia. For the purpose of exploring roles of the dysregulated long non-coding RNA (lncRNA) in NPC, we identified a novel lncRNA LINC00669 with an apparent negative correlation to the overall survival from human NPC mRNA expression profiling databases. We further performed RNA pulldown coupled with mass spectrum to find out its target protein, and applied a series of in vitro and in vivo loss-and-gain-of function assays to investigate its oncogenic roles in NPC tumor development and progression. Our results demonstrated that LINC00669 competitively binds to the key JAK/STAT signaling pathway suppressor SOCS1, and insulates it from imposing ubiquitination modification on the pathway component of STAT1, which leads to its abnormal stabilization and activation. The activated STAT1 is then transferred into the nucleus and initiates the transcription of genes related to proliferation and invasion. In summary, our study reveals that the cytoplasmic resident lncRNA LINC00669 confers malignant properties on NPC cancer cells by facilitating a persistent activation of the JAK/STAT signaling pathway. Findings in the current study shed lights on prospects for treating NPC using strategies targeting the novel regulator of the JAK/STAT signaling.

Objective: To provide experimental evidence for the folate receptor 1 (FOLR1) mediated targeted cancer therapy and resistance reversal, the FOLR1 expression differences in nasopharyngeal carcinoma cells (CNE-1) and immortalized normal nasopharyngeal cells (NP69) and the correlation between FOLR1 expression and paclitaxel resistance index in nasopharyngeal carcinoma were investigated., Methods: The expressions of FOLR1 in CNE-1, CNE-1/Taxol (paclitaxel-resistance cells) and NP69 was detected by cDNA microarray, reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry. Proliferation inhibition rates of CNE-1 and CNE-1/Taxol cells were measured by colony formation assay after treated by short interfering RNA (siRNA) of FOLR1., Results: The expressions of FOLR1 gene in CNE-1/Taxol cells and CNE-1 cells were 2636.0 and 176.0, respectively. The expression of FOLR1 was not detected in the NP69 by semi-quantative RT-PCR and Western blot. The high expression of FOLR1 in CNE-1/Taxol was verified by semi-quantative RT-PCR, and its expression level was positively correlated to the degree of drug-resistance (r(2) = 0.8719). The results were also validated by Western blot and immunocytochemistry. The sensitivity of CNE-1/Taxol to paclitaxel significantly increased after inhibition of FOLR1 gene expression by siRNA, and its IC(50) value was decreased by 59.6% (t = 6.92, P < 0.01)., Conclusions: The expression of FOLR1 is closely related to the occurrence of NPC and Taxol resistance. FOLR1 gene may be one of the important target molecules in NPC treatment and reversion of the paclitaxel-resistance in NPC.

Objective: To evaluate the effect of genomic instability on prognostics in nasopharyngeal carcinoma., Methods: Genomic instability was assessed by inter-simple sequence repeats polymerase chain reaction (inter-SSR PCR) in 38 patients with nasopharyngeal carcinoma. Characterization and verification of band alterations shared in different tumors were carried out by sequencing and nest PCR., Results: Thirty-one (81.6%) of the 38 patients showed genomic altercations, and genomic instability index ranged 0 to 16.2 percent. A gain-based genomic damage shared in 6 tumors was identified on chromosome 6q27. Genomic alteration was significantly more in patients less than 5-year survival than those with more than 5-year survival (P<0.05)., Conclusion: Genomic instability can be an early event marker in carcinogenesis of nasopharyngeal carcinoma. Aggravation of genomic alterations is a poor prognosis for cancer recovery.

To isolate and clone the tumor suppressor gene on chromosomal region 7q32 that corelated with the occurrence of human NPC, we detected the genotype of polymorphic microsatellite markers on 7q32 in 24 nasopharyngeal carcinoma biopsies and matched normal lymphocyte DNA. LOH was found in 30% biopsies. Using differential RT-PCR and Northern hybridization we compared the expression level of 20 EST on 7q32 between NPC cell line HNE1 and primary culture of normal nasopharyngeal epithelial cell, and found AA070437 EST expressed high in primary culture of normal nasopharyngeal epithelial cell, but very low in HNE1. Differential RT-PCR (dRT-PCR) analysis showed that the expression level of AA070437 was lower in 30.7% NPC biopses than in normal cell. Differential PCR (dPCR) showed that allelic loss of AA070437 was observed in 29.1% NPC biopses. This EST is a part of sequence of a new gene compared with GeneBank database. Our results showed that AA070437 EST negatively related with the occurrence of human NPC is a candidate of tumor suppressor gene of NPC on 7q32.

T lymphocyte subsets, IL-2 production and IL-2 receptor expression were detected in PBLs of 31 NPC patients and 28 normal subjects and of normal PBLs populations under the influence of serum of NPC patients. The results were as follows: CD4+ and IL-2 receptor expression, CD4+:CD8+ ratios and IL-2 production were significantly depressed and CD8+-significantly elevated in PBLs of NPC patients before radiation and of normal PBLs populations under the influence of the serum of NPC patients. CD8+ was significantly decreased and CD4+, IL-2 production and IL-2 receptor expression were depressed in patients after radiation. These suggest that cellular immunity and immunoregulation are impaired in NPC patients before and after radiation.