Nasopharyngeal Carcinoma Carcinogenesis Research Articles

NKILA represses nasopharyngeal carcinoma carcinogenesis and metastasis by NF-κB pathway inhibition

The role of long non-coding RNA (lncRNA) in the progression of Nasopharyngeal carcinoma (NPC) has not been fully elucidated. The study was designed to explore the functional role of NKILA, a newly identified lncRNA, in the progression of NPC. We performed a lncRNA expression profile microarray using four NPC and paired para-cancerous tissues. NKILA was identified as a potential functional lncRNA by this lncRNA expression profile. We used 107 paraffin-embedded NPC tissues with different TNM stages to detect the expression of NKILA and analyzed the survival data by Log-rank test and Cox regression. The role of NKILA and its underlying mechanisms in the progression of NPC were evaluated by a series of experiments in vitro and vivo by silencing or expressing NKILA. Compared with control tissues, NKILA expression was identified to be decreased in NPC tissues. Low NKILA expression was correlated with unfavorable clinicopathological features and predicted poor survival outcome in NPC patients. After adjusting for potential confounders, low expression of NKILA was confirmed to be an independent prognostic factor correlated with poor survival outcomes. Furthermore, we found that NKILA overexpression in high-metastatic-potential NPC cells repressed motile behavior and impaired the metastatic capacity in vitro and in vivo. In contrast, RNAi-mediated NKILA depletion increased the invasive motility of cells with lower metastatic potential. Further experiments demonstrated that NKILA regulated the metastasis of NPC through the NF-κB pathway. Taken together, NKILA plays vital roles in the pathogenesis of NPC. The unique histological characteristics of NPC indicate that local inflammation plays a vital role in carcinogenesis of nasopharyngeal carcinoma.

MicroRNA-103 promotes nasopharyngeal carcinoma through targeting TIMP-3 and the Wnt/β-catenin pathway.

To verify how microRNA-103 (miR-103) is involved in nasopharyngeal carcinoma (NPC) development. Research on the relationship between miR-103 and NPC. Tissue inhibitor of metalloproteinases-3 (TIMP-3) was identified as the theoretical target gene of miR-103, and its regulatory mechanism in NPC was explored by quantitative reverse transcription polymerase chain reaction, Western blot, MTT, transwell, and luciferase reporter assays. MiR-103 was upregulated whereas TIMP-3 was markedly decreased in NPC tissue samples. Ectopic expression of miR-103 promoted NPC cell viability, migration, and invasion. In vitro assay showed that TIMP-3 recovered miR-103-mediated promotion of NPC cell viability, migration, and invasion. The expression of Wnt/β-catenin pathway markers (β-catenin and cyclin D1) were enhanced after miR-103 overexpression. MiR-103 might play a key role in NPC carcinogenesis by targeting TIMP-3 and affecting the Wnt/β-catenin pathway. NA Laryngoscope, 130:E75-E82, 2020.

Tumor-educated platelet miR-34c-3p and miR-18a-5p as potential liquid biopsy biomarkers for nasopharyngeal carcinoma diagnosis.

Background: Nasopharyngeal carcinoma (NPC) is the common malignant tumor of nasopharynx in southern China and other southeastern Asian countries. MicroRNAs (miRNAs) have been shown to play important roles in carcinogenesis. Recently, miR-34c-3p and miR-18a-5p have been found to be involved in carcinogenesis of NPC. Furthermore, platelets in NPC patients may acquire RNAs from NPC cells and turn into “tumor-educated platelet (TEP)”, which may serve as potential biomarkers for a diagnosis of NPC. However, the expression profiles of TEP miR-34c-3p and miR-18a-5p in NPC patients and their diagnostic values are yet to be determined.Aims: To investigate expression levels of TEP miR-34c-3p and miR-18a-5p and determine their diagnostic values for NPC.Materials and methods: Relative quantitative real-time PCR was used to determine the expression levels of TEP miR-34c-3p and miR-18a-5p in NPC patients (n=54) as compared to normal subjects (n=36). The receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic values of TEP miR-34c-3p and miR-18a-5p for NPC.Results: The expression levels of TEP miR-34c-3p and miR-18a-5p were significantly higher in NPC patients as compared to healthy subjects. The ROC analysis showed that the area under the ROC curve (AUC), sensitivity, specificity and accuracy for TEP miR-34c-3p, miR-18a-5p, or a combination of both miRNAs for NPC diagnostic tests were 0.952, 94.44%, 86.11%, 91.11%, or 0.884, 85.19%, 86.11%, 85.55%, or 0.954, 92.59%, 86.11%, 90.00%, respectively. No correlation was found between expression levels of TEP miR-34c-3p or miR-18a-5p and patients’ demographic variables and their NPC tumor/node/metastasis stages. The positive rates of TEP miR-34c-3p and miR-18a-5p for NPC diagnosis were 93.8% and 87.5%, respectively, which were significantly higher than Epstein-Barr virus DNA with a positive rate of 66.7%.Conclusion: The expression levels of TEP miR-34c-3p and miR-18a-5p are upregulated in NPC, rendering a significant clinical value for NPC diagnosis. The TEP miRNAs might serve as a novel type of liquid biopsies for NPC diagnosis.

Long non-coding RNA 520 is a negative prognostic biomarker and exhibits pro-oncogenic function in nasopharyngeal carcinoma carcinogenesis through regulation of miR-26b-3p/USP39 axis

Long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigenesis, especially nasopharyngeal carcinoma (NPC). In present study, we aims to investigate the role and mechanism of LINC00520 in the NPC carcinogenesis. Results indicated that LINC00520 was significantly increasing in NPC tissues and cells in comparison to their corresponding controls. Moreover, the aberrant overexpression of LINC00520 indicated the poor prognosis of NPC patients. Silence of LINC00520 was able to repress NPC cell growth in vitro while overexpression of LINC00520 inversed this process. Moreover, in vivo tumor xenografts were establishing using CNE-1/SUNE-1 cells to investigate the function of LINC00520 in NPC tumorigenesis. Rescue assay was conducting to further confirm that LINC00520 contributed to NPC progression by regulating miR-26b-3p/ubiquitin-specific protease 39 (USP39) signal pathway. Taken together, our study discovered the oncogenic role of LINC00520 in clinical specimens and cellular experiments, showing the potential LINC00520/miR-26b-3p/USP39 pathway. This results and findings provide a novel insight for NPC tumorigenesis.

Epstein-Barr virus-encoded LMP1 regulated Pim1 kinase expression promotes nasopharyngeal carcinoma cells proliferation.

BackgroundEpstein–Barr virus-encoded LMP1 plays a critical role in the carcinogenesis of nasopharyngeal carcinoma (NPC), but the mechanism remains elusive. We aimed to analyze the expression and clinical pathological significance of provirus integration site for Moloney murine leukemia virus 1 (Pim1) in clinical NPC, and to elucidate the effect of LMP1 on Pim1 expression and its mechanism.MethodsImmunohistochemical staining was used to detect the expression of Pim1 in clinical NPC tissues and control nasopharyngeal chronic inflammation (NPI) tissues, and the correlation between Pim1 and clinical parameters of NPC patients was analyzed. The LMP1 stable expression cell line CNE1-LMP1-OV was constructed through infecting the well-differentiated nasopharyngeal carcinoma cells CNE1 with LMP1 overexpressing lentivirus. Then the in vivo experiments were conducted.ResultsAmong 89 NPC patients, 48 cases (53.93%) were positive for Pim1, while only one case was Pim1 positive in 15 NPI controls (6.67%). Pim1 expression was not correlated with gender, age, smoking status and clinical classification of NPC patients, but positively correlated with T, N and M classification. CNE1-LMP1-OV cell line was successfully established, which displayed a higher cell proliferation ability and Pim1 expression. NF-κB inhibitor PDTC, PKC inhibitor GF109203X and STAT3 inhibitor Stattic significantly attenuated LMP1-induced Pim1 expression, and while AP-1 inhibitor SR11302 showed no inhibitory effect. Interestingly, Pim1 inhibitor quercetagetin significantly inhibited the proliferation of CNE1-LMP1-OV cells.ConclusionLMP1 mediates Pim1 expression through NF-κB, PKC and STAT3 signaling, which promotes the proliferation of NPC cells and participate in the clinical progression of NPC.

CHL1 suppresses tumor growth and metastasis in nasopharyngeal carcinoma by repressing PI3K/AKT signaling pathway via interaction with Integrin β1 and Merlin.

Deletion of Chromosome 3p is one of the most frequently detected genetic alterations in nasopharyngeal carcinoma (NPC). We reported the role of a novel 3p26.3 tumor suppressor gene (TSG) CHL1 in NPC. Down-regulation of CHL1 was detected in 4/6 of NPC cell lines and 71/95 (74.7%) in clinical tissues. Ectopic expressions of CHL1 in NPC cells significantly inhibit colony formation and cell motility in functional study. By up-regulating epithelial markers and down-regulating mesenchymal markers CHL1 could induce mesenchymal-epithelial transition (MET), a key step in preventing tumor invasion and metastasis. CHL1 could also cause the inactivation of RhoA/Rac1/Cdc42 signaling pathway and inhibit the formation of stress fiber, lamellipodia, and filopodia. CHL1 could co-localize with adhesion molecule Integrin-β1, the expression of CHL1 was positively correlated with Integrin-β1 and another known tumor suppressor gene (TSG) Merlin. Down-regulation of Integrin-β1 or Merlin was significantly correlated with the poor survival rate of NPC patients. Further mechanistic studies showed that CHL1 could directly interact with integrin-β1 and link to Merlin, leading to the inactivation of integrin β1-AKT pathway. In conclusion, CHL1 is a vital tumor suppressor in the carcinogenesis of NPC.

Placenta specific 8 gene induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via the TGF-β/Smad pathway

The present study aimed to investigate the effects and mechanisms of PLAC8 on the epithelial-mesenchymal transition (EMT) of Nasopharyngeal carcinoma (NPC). The expression of PLAC8 in NPC and nasopharyngitis (NPG) tissues from 150 patients was determined using immunohistochemistry. The levels of PLAC8 in five NPC cell lines and nasopharyngeal permanent epithelial cell line were measured using western blotting. We then knocked out or overexpressed PLAC8 in CNE2 cells. Cell proliferation, wound healing, migration, and invasion assays were used to analyze the effects of PLAC8 on the proliferation, migration, and invasion in vivo and vitro. The results showed that the expression of PLAC8 was much higher in NPC tissues than in NPG tissues. The expression of PLAC8 was higher in all the cell lines than in the nasopharyngeal permanent epithelial cells. PLAC8 knockout resulted in significant decreases in cell proliferation, migration, and invasion; associated with lower protein levels of N-cadherin; and increased levels of E-cadherin. Overexpression of PLAC8 had the opposite effect. Furthermore, knockout of PLAC8 inactivated TGF-β/SMAD signaling pathway and suppressed the growth of NPC xenografts. PLAC8 may promote the carcinogenesis and EMT of NPC via the TGF-β/Smad pathway, which suggests that PLAC8 may be a potential biomarker for NPC.

Interleukin-18 promoter genotype is associated with the risk of nasopharyngeal carcinoma in Taiwan.

BackgroundThe incidence rate of nasopharyngeal carcinoma (NPC) has been documented to be high in Southeast Asia. Interleukin-18 (IL-18) is a multifunctional cytokine that augments interferon-γ production and acts as an important immunomediator in the development of several types of cancer.Patients and methodsThis case–control study evaluated the role of IL-18 in NPC at the DNA level by genotyping its promoter polymorphisms at positions -656, -607, and -137 in a Taiwanese population. A total of 176 patients with NPC and age- and gender-matched 352 noncancer controls were included in this study.ResultsThe CC genotype of the IL-18-607 polymorphism was found to be associated with significantly decreased risks of NPC compared to the AA genotype (crude OR =0.50, 95% CI =0.29–0.84, P=0.0093). This significant difference persisted even in the dominant and recessive models. A significantly lower C allele frequency at position -607 was detected in the NPC group(41.8% vs 50.3%; OR =0.77; 95% CI =0.63–1.04, P=0.0089). Regarding IL-18-656 and -137 polymorphisms, there were no differential distributions of their genotypes between the NPC and control groups. After substratification of the subjects according to their smoking, alcohol consumption, and areca chewing status, the genotype distribution of the IL-18-607 polymorphism was found to be different only among nonsmokers between the NPC and control subgroups.ConclusionThis study suggests that IL-18 plays an important role in the carcinogenesis of NPC in Taiwan and that the genotype–phenotype correlation of IL-18-607 polymorphism and its contribution to NPC need to be investigated further.

Long non-coding RNA 319 facilitates nasopharyngeal carcinoma carcinogenesis through regulation of miR-1207-5p/KLF12 axis

Long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigeneses, especially nasopharyngeal carcinoma (NPC). In present study, we aim to investigate the role of LINC00319 in the NPC carcinogenesis. It was indicated that LINC00319 was markedly increased in NPC tissues and cells in comparison to their corresponding controls. Moreover, the aberrant overexpression of LINC00319 indicated the poor prognosis of NPC patients. Silence of LINC00319 was able to suppress NPC cell growth in vitro while overexpression of LINC00319 inversed this process. Moreover, in vivo tumor xenografts were established using CNE-1/SUNE-1 cells to investigate the function of LINC00319 in NSCLC tumorigenesis. Rescue assay was performed to further confirm that LINC00319 contributed to NPC progression by regulating miR-1207-5p/KLF12 signal pathway. Taken together, our study discovered the oncogenic role of LINC00319 in clinical specimens and cellular experiments, showing the potential LINC00319/miR-1207-5p/KLF12 pathway. This results and findings provide a novel insight for NPC tumorigenesis.

Long non-coding RNA ZNF674-1 acts as a cancer suppressor in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is the most frequently occurring carcinoma of the head and neck. The complexity of NPC makes it difficult for it to be diagnosed and treated at an early stage. Certain long non-coding RNAs (lncRNAs) are closely associated with the carcinogenesis of NPC. In the present study, the expression of lncRNA ZNF674-1 in NPC tissues and an NPC cell line was analyzed and was revealed to be downregulated compared with normal tissues and cells. When the expression of lncRNA ZNF674-1 was reduced in NPC cells, the proliferation, migration and invasion of these cells was promoted, whereas the apoptosis of these cells was decreased. On the contrary, when overexpressed, the expression of lncRNA ZNF674-1 inhibited the proliferation, invasion and migration of cells, but promoted cell apoptosis. The results of the present study reveal that the lncRNA ZNF67-1 may restrain the carcinogenesis of NPC, and may also serve as a potential biomarker for the early diagnosis and treatment of NPC.

Perspective: Contribution of Epstein-Barr virus (EBV) Reactivation to the Carcinogenicity of Nasopharyngeal Cancer Cells.

Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma derived from the epithelium of the post-nasal cavity, with a unique geographic and ethnic distribution. Epstein–Barr virus (EBV) is an etiological agent of NPC, but how it contributes to carcinogenesis is not completely clear. Although it is thought that EBV latency participates in the development of NPC, increasing evidence reveals that the lytic cycle also plays an important role in the carcinogenic process. In this review, we summarize our recent studies on how EBV reactivation causes genomic instability and accelerates tumorigenesis in epithelial cells. The roles of three lytic genes, namely, BRLF1, BGLF5 and BALF3, in this process are also introduced. Moreover, blocking EBV reactivation using natural compounds may help delay the progression of NPC tumorigenesis. These studies provide a new insight into NPC carcinogenesis and raise the possibility that inhibition of EBV reactivation may be a novel approach to prevent the relapse of NPC.

Nasopharyngeal carcinoma: A review of current updates

Nasopharyngeal carcinoma (NPC) is a rare malignancy worldwide, but it is endemic in a few areas including Southern China, Southeast Asia, North Africa and the Arctic. The underlying mechanisms behind this remarkable geographic distribution remain unclear. Although Epstein-Barr virus (EBV) infection has been suggested as a necessary cause of undifferentiated NPC, EBV itself is not sufficient to cause this malignancy. Other co-factors, such as environmental risk factors, and/or genetic susceptibility, may interact with EBV to play a role in the carcinogenesis of NPC. Survival rates differ significantly between NPC patients in early stages and late stages. Due to the close associations between EBV infection and NPC risk, EBV-related biomarkers have been used for early detection and screening for NPC in a few high-incidence areas. In the present review article the latest updates are discussed.

Lack of association between cigarette smoking and Epstein Barr virus reactivation in the nasopharynx in people with elevated EBV IgA antibody titres

BackgroundSubjects with elevated Epstein-Barr virus (EBV) immunoglobulin A (IgA) titers have a higher risk of developing nasopharyngeal carcinoma (NPC), indicating that reactivation of EBV in the local mucosa might be important for NPC carcinogenesis. Cigarette smoking appears to be one of the environmental risk factors for NPC. However, it remains unclear whether smoking-induced nasopharyngeal carcinogenesis acts through reactivating EBV in the nasopharyngeal mucosa. Therefore, this study aims to investigate the association between cigarette smoking and nasopharyngeal EBV reactivation in a NPC high-risk population.MethodsA NPC high-risk cohort study, established from a population-based NPC screening program of 22,816 subjects, consisted of 1045 subjects with elevated serum IgA antibodies against EBV viral capsid antigen (VCA/IgA). Among high-risk subjects, information on detailed cigarette smoking history was collected among 313 male subjects. The associations between cigarette smoking and EBV antibody levels, EBV DNA load of the nasopharynx were analyzed.ResultsNo significant association was observed between either nasopharyngeal EBV DNA load or serum VCA/IgA titers and smoking status, age at smoking initiation, daily smoking intensity, smoking duration, cigarette type, or pack-years of smoking. Cigarette smoking characteristics in all subgroups did not correlate with nasopharyngeal EBV DNA positivity or EBV VCA/IgA seropositivity.ConclusionsIn a population at high risk of NPC, our study suggests that cigarette smoking is neither associated with nasopharyngeal EBV DNA load nor serum VCA/IgA antibody level. Smoking-associated NPC carcinogenesis may act through other mechanisms than reactivating nasopharyngeal EBV replication.

Preparation of anti-NYD-SP8 rabbit polyclonal antibody and its application in the analysis of NYD-SP8 expression in nasopharyngeal carcinoma cell lines and clinical tissues.

NYD-SP8 is a recently identified protein, the biological characteristics of which are still unclear. The aim of this study was to prepare an anti-NYD-SP8 rabbit polyclonal antibody and investigate the expression of NYD-SP8 in human nasopharyngeal carcinoma cell lines and nasopharyngeal carcinoma tissues. The anti-NYD-SP8 rabbit polyclonal antibody was prepared and ELISA was performed to assess the antibody titer. With this antibody, the NYD-SP8 expression in four nasopharyngeal carcinoma cell lines, CNE1, CNE2, 5-8F and 6-10B, was examined by Western blot and its expression in clinical tissues was also assessed by immunohistochemistry. The anti-NYD-SP8 rabbit polyclonal antibody with a high titer was successfully prepared. Western blot showed higher NYD-SP8 expression in CNE2 and 6-10B cells and lower expression in CNE1 and 5-8F cells. Immunohistochemistry demonstrated overexpression of NYD-SP8 in nasopharyngeal carcinoma tissue while the expression in normal nasopharyngeal tissue was negligible. Our anti-NYD-SP8 rabbit polyclonal antibody can be used both for Western blot and immunohistochemistry, and can be a valuable tool to investigate the function and distribution of NYD-SP8. The different NYD-SP8 expression in various nasopharyngeal carcinoma cell lines indicated its complicated functions at different biological stages. The overexpression of NYD-SP8 in clinical nasopharyngeal carcinoma tissue indicated that it could play an important role in nasopharyngeal carcinoma carcinogenesis.

Rediscovery of NF‐κB signaling in nasopharyngeal carcinoma: How genetic defects of NF‐κB pathway interplay with EBV in driving oncogenesis?

Nasopharyngeal carcinoma (NPC) is a unique EBV-associated subtype of head and neck cancer, which has the highest incidence in Southern China and eastern South Asia. The interaction between genetic risk factors and environmental challenge, have been considered to contribute to the development of nasopharyngeal carcinogenesis. Constitutive activation of NF-κB signaling has been seen in NPC tissues and is associated with unfavorable prognosis. Recently, several whole exome sequencing study consistently revealed that high frequency mutations of NF-κB pathway negative regulators is common in nasopharyngeal carcinoma, which reinforce the importance of NF-κB driving oncogenesis. This review focuses on the current state of research in role of NF-κB in NPC carcinogenesis. We summarized the newly identified loss of function (LOF) mutations on NF-κB negative regulators leading to it's activation bypass LMP-1 stimulation. We discussed the critical role of NF-κB activation in immortalization and transformation of nasopharygeal epithelium. We also depicted how NF-κB signaling mediated chronic inflammation contribute to persistent EBV infection, immune evasion of EBV infected cells, metabolic reprogramming, and cancer stem cells (CSCs) formation in NPC. Lastly, we discussed the clinical resonance of targeting NF-κB for NPC precise therapy.

Long non-coding RNA FOXD2-AS1 aggravates nasopharyngeal carcinoma carcinogenesis by modulating miR-363-5p/S100A1 pathway

Long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigenesis, especially nasopharyngeal carcinoma (NPC). In present study, we aim to investigate the role of lncRNA FOXD2-AS1 in the NPC carcinogenesis. It was indicated that FOXD2-AS1 was markedly increased in NPC tissues and cells in comparison to their corresponding controls. Moreover, the aberrant overexpression of FOXD2-AS1 indicated the poor prognosis of NPC patients. Silence of FOXD2-AS1 was able to repress NPC cell growth in vitro while overexpression of FOXD2-AS1 inversed this process. Moreover, in vivo tumor xenografts were established using CNE-1/SUNE-1 cells to investigate the function of FOXD2-AS1 in NSCLC tumorigenesis. Rescue assay was performed to further confirm that FOXD2-AS1 contributed to NPC progression by regulating miR-363-5p/S100A1 signal pathway. Taken together, our study discovered the oncogenic role of FOXD2-AS1 in clinical specimens and cellular experiments, showing the potential FOXD2-AS1/miR-363-5p/S100A1 pathway. This results and findings provide a novel insight for NPC tumorigenesis.

Long Noncoding RNA LINC0086 Functions as a Tumor Suppressor in Nasopharyngeal Carcinoma by Targeting miR-214.

Nasopharyngeal carcinoma (NPC) is a distinct head and neck cancer, which is occurring at a high frequency in Southern China. Emerging studies have shown that long noncoding RNAs (lncRNAs) play a critical role in carcinogenesis and progression. In this study, we established a comprehensive lncRNA profile in NPC and found that 35 lncRNAs were differentially expressed in NPC. We found that LINC0086 was decreased in NPC patient serum samples and tissues. The Kaplan–Meier survival curve showed that patients with high LINC0086 expression had a higher survival rate than those with low LINC0086 expression. LINC0086 expression was associated with NPC histological grade, lymph node metastasis, and clinical stage. Upregulation of LINC0086 inhibited cancer cell proliferation and promoted apoptosis. In addition, upregulation of LINC0086 dramatically decreased the expression of miR-214, an oncogene in several cancers, in C666-1 and HK-1 cells. An miR-214 binding site was found in the 3′-UTR of LINC0086. We also validated that both miR-214 and LINC0086 presented in the RISC complex, demonstrating that LINC0086 could decrease miR-214 expression by directly interacting with miR-214. Furthermore, the suppressive effects of LINC0086 on NPC cell growth were reversed by overexpression of miR-214 in vitro and in vivo. Thus, our study reports a novel mechanism underlying NPC carcinogenesis and provides a potential novel diagnosis and treatment biomarker for NPC.

The effects of microRNA-98 inhibits cell proliferation and invasion by targeting STAT3 in nasopharyngeal carcinoma

MicroRNA-98 (miR-98) is downregulated in many tumors, and is closely related to tumor progression. In addition, it shows anticarcinogenic functions in various tumor. However, few study show that the biological function and regulatory mechanisms of miR-98 in nasopharyngeal carcinoma (NPC) progression. The identification and its target genes which regulate by dysregulated miRNAs may strengthen our understanding of the molecular mechanisms of NPC. In this study, we observe that miR-98 is not only significantly reduced in NPC tissues, but also decreased markedly in NPC cell lines. Moreover, silencing miR-98 expression studies not only show miR-98 induced cell proliferation, migration and invasion in vitro, but also it promoted xenograft tumor growth in vivo in NPC. Furthermore, western blot assay was used to detected the level of STAT3 protein and we demonstrate that miR-98 regulate cells poliferation, migration and invasion through directly modulating functional target STAT3 by directly binding its 3′-UTR. These findings illustrate miR-98 as a anticarcinogenic functions through targeting STAT3, the miR-98/STAT3 pathway gives new clues for understanding NPC carcinogenesis and provides novel therapeutic targetsfor NPC.

Detection of nasopharyngeal carcinoma susceptibility with single nucleotide polymorphism analysis using next-generation sequencing technology.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer with high incidence in South China and East Asia. To provide a theoretical basis for NPC risk screening and early prevention, we conducted a meta-analysis of relevant literature on the association of single nucleotide polymorphisms (SNP)s with NPC susceptibility. Further, expression of 15 candidate SNPs identified in the meta-analysis was evaluated in a cohort of NPC patients and healthy volunteers using next-generation sequencing technology. Among the 15 SNPs detected in the meta-analysis, miR-146a (rs2910164, C>G), HCG9 (rs3869062, A>G), HCG9 (rs16896923, T>C), MMP2 (rs243865, C>T), GABBR1 (rs2076483, T>C), and TP53 (rs1042522, C>G) were associated with decreased susceptibility to NPC, while GSTM1 (+/DEL), IL-10 (rs1800896, A>G), MDM2 (rs2279744, T>G), MDS1-EVI1 (rs6774494, G>A), XPC (rs2228000, C>T), HLA-F (rs3129055, T>C), SPLUNC1 (rs2752903, T>C; and rs750064, A>G), and GABBR1 (rs29232, G>A) were associated with increased susceptibility to NPC. In our case-control study, an association with increased risk for NPC was found for the AG vs AA genotype in HCG9 (rs3869062, A>G). In addition, heterozygous deletion of the GSTM1 allele was associated with increased susceptibility to NPC, while an SNP in GABBR1 (rs29232, G>A) was associated with decreased risk, and might thus have a protective role on NPC carcinogenesis. This work provides the first comprehensive assessment of SNP expression and its relationship to NPC risk. It suggests the need for well-designed, larger confirmatory studies to validate its findings.

Long non-coding RNA LOC100129148 functions as an oncogene in human nasopharyngeal carcinoma by targeting miR-539-5p.

Emerging studies have shown that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and progression, including human nasopharyngeal carcinoma (NPC). The correlation between lncRNAs expression and NPC development has not been well identified in the recent literature. Recently, high-through put analysis reveals that LOC100129148 is highly expressed in NPC. However, whether the aberrant expression of LOC100129148 in NPC is corrected with tumorigenesis or prognosis has not been investigated. Herein, we identified that LOC100129148 was up-regulated in NPC tissues and cell lines, and higher expression of LOC100129148 resulted in a markedly poorer survival time. Over-expressed LOC100129148 favored, but silenced LOC100129148 hampered cell proliferation in NPC cells. Additionally, LOC100129148 enhanced the KLF12 expression through functioning as a competitive ‘sponge’ for miR-539-5p. Thus, our study reports a novel mechanism underlying NPC carcinogenesis, and provides a potential novel diagnosis and treatment biomarker for NPC.