Background: Among head and neck squamous cell carcinomas (HNSCCs), hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis. Iron metabolism, which plays a crucial role in tumor progression, is mainly regulated by alterations to genes and post-transcriptional processes. The recent discovery of the N6-methyladenosine (m 6 A) modification has expanded the realm of previously undiscovered post-transcriptional gene regulation mechanisms in eukaryotes. Many studies have demonstrated that m 6 A methylation represents a distinct layer of epigenetic deregulation in carcinogenesis and tumor proliferation. However, the status of m 6 A modification and iron metabolism in HPSCC remains unknown. Methods: Bioinformatics analysis, sample analysis, and transcriptome sequencing were performed to evaluate the correlation between m 6 A modification and iron metabolism. Iron metabolic and cell biological analyses were conducted to evaluate the effect of the m 6 A reader YTHDF1 on HPSCC proliferation and iron metabolism. Transcriptome-wide m 6 A-seq and RIP-seq data were mapped to explore the molecular mechanism of YTHDF1 function in HPSCC. Results: YTHDF1 was found to be closely associated with ferritin levels and intratumoral iron concentrations in HPSCC patients at Sir Run Run Shaw Hospital. YTHDF1 induced-HPSCC tumorigenesis depends on iron metabolism in vivo in vitro . Mechanistically, YTHDF1 methyltransferase domain interacts with the 3'UTR and 5'UTR of TRFC mRNA, then further positively regulates translation of m 6 A-modified TFRC mRNA. Gain-of-function and loss-of-function analyses validated the finding showing that TFRC is a crucial target gene for YTHDF1-mediated increases in iron metabolism. Conclusion: YTHDF1 enhanced TFRC expression in HPSCC through an m 6 A-dependent mechanism. From a therapeutic perspective, targeting YTHDF1 and TFRC-mediated iron metabolism may be a promising strategy for HPSCC.

Recent studies have reported that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and progression. LncRNA-LET, a recently identified lncRNA, has been shown to be a tumor suppressor in hepatocellular carcinoma. However, the expression and functional of lncRNA-LET in other type of cancers remain largely unknown. In this study, we found that lncRNA-LET was significantly downregulated in nasopharyngeal carcinoma (NPC) tissues compared with corresponding normal tissues. Decreased LET expression is significantly correlated with advanced clinical stage, larger tumor size, increased lymph node tumor burden, and poor survival of NPC patients. Gain- and loss-of-function experiments demonstrated that enhanced LET expression inhibited NPC cells proliferation and induced cell apoptosis. By contrast, the knockdown of LET promoted NPC cells proliferation and inhibited cell apoptosis. Importantly, we found lncRNA-LET is transcriptional repressed by EZH2-mediated H3K27 histone methylation on the LET promoter. The expressions of EZH2 and lncRNA-LET are significantly inversely correlated in NPC tissues. Collectively, these findings indicate a pivotal role for lncRNA-LET in NPC cell proliferation and apoptosis, and reveal an epigenetic mechanism for lncRNA-LET dysregulation.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is an emergency disease requiring immediate diagnosis and treatment. the incidence of iSSnHL in the Western countries' population was estimated to 5-20 per 100,000 inhabitants. The etiology of ISSNHL remains unknown. Its pathogenesis is most often suggested to be due to a disturbed microcirculation and infection. previous studies have reported that comorbidities, including hypertension, diabetes mellitus (DM), and hyperfibrinogenemia are risk factors of ISSNHL. This study aimed at investigating the clinical characteristics, laboratory parameters and comorbidities of patients with iSSnHL. our study suggests that the annual incidence of iSSnHL in China mainland is 19 per 100 000. The clinical characteristics and prevalence of comorbidities of ISSNHL patients are different according to age distribution and hearing results. Moreover, the patients with vertigo, hypertension, DM and high TG suffered more often from severe hearing loss compared with the counterparts. this indicates that the cardiovascular and metabolic diseases (hypertension and hyperlipidemia) appeared to be closely associated with the occurrence and severity of iSSnHL.

As a component of the MRN (MRE11/RAD50/NBS1) complex, NBS1 plays an important role in cellular response to DNA damage and the maintenance of chromosomal integrity. The NBS1 E185Q polymorphism (8360G>C, rs1805794) has been frequently studied in some cancers with discordant results, but its association with nasopharyngeal carcinoma (NPC) in Chinese population has not been investigated. Moreover, there is no report about the association between NBS1 3 0 UTR variant rs2735383 and the risk of NPC. A multiple center case-control analysis was performed to assess the association between NBS1 polymorphisms and NPC risk in Eastern and Southern Chinese population. The genotypes and haplotypes were determined in 1052 cases and 1168 controls and the associations with risk of NPC were estimated by logistic regression. Cell migration assays were performed in 24-well transwell chambers to detect the effects of NBS1 E185Q SNP on cell migration. We observed significant difference in genotype frequencies at the rs1805794 C/G site between cases and controls (P trend < 0.0001). The C allele increases the risk for invasive disease or metastatic disease, compared with G allele. More over, CNE-2 cells (NPC cell line) transfected with pcDNA-NBS1-185Q (8360CC) had significantly higher migration levels than those transfected with pcDNA-NBS1-185E (8360GG) (P ¼ 0.024). These findings suggest that E185Q polymorphism in NBS1 may be a genetic modifier for the occurrence and aggression of NPC. ß

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