microRNA-342-3p targets FOXQ1 to suppress the aggressive phenotype of nasopharyngeal carcinoma cells.

BACKGROUND: microRNA (miR)-342-3p is frequently dysregulated in human cancers. In the present study, we aimed to explore the expression, prognostic significance, and biological relevance of miR-342-3p in nasopharyngeal carcinoma (NPC). METHODS: We examined miR-342-3p expression in 79 paired NPC specimens and corresponding normal tissues and analyzed its prognostic impact on overall survival of NPC patients. Gain- and loss-of-function experiments were conducted to determine the biological roles of miR-342-3p. RESULTS: Compared with matched normal nasopharyngeal tissues, miR-342-3p was significantly downregulated in NPC (P = 0.0038). Low miR-342-3p expression was significantly correlated with reduced overall survival (P = 0.0084). Ectopic expression of miR-342-3p significantly suppressed proliferation, colony formation, and invasion of NPC cells. In contrast, depletion of miR-342-3p facilitated NPC cell proliferation and invasion. In vivo xenograft studies confirmed that overexpression of miR-342-3p restrained the growth of NPC xenograft tumors. Mechanistically, FOXQ1 served as a functional target of miR-342-3p. There was a significantly negative correlation between miR-342-3p and FOXQ1 expression (r = - 0.487, P = 0.004) in NPC specimens. Overexpression of FOXQ1 rescued the inhibitory effects of miR-342-3p on NPC cell growth and invasion. CONCLUSIONS: miR-342-3p downregulation predicts poor prognosis in NPC patients and shows suppressive activity against NPC growth and invasion through repression of FOXQ1. Restoration of miR-342-3p may represent a potential therapeutic strategy for NPC.

Seed amplification assay of nasal swab extracts for accurate and non-invasive molecular diagnosis of neurodegenerative diseases.

Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx. Dysosmia is regarded as an early sign of coronavirus disease 2019 (COVID-19), and nasal swabs are the gold standard for the detection. By nasal swabs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids can be cyclically amplified and detected using real-time reverse transcriptase-polymerase chain reaction after sampling. Similarly, olfactory dysfunction precedes the onset of typical clinical manifestations by several years in prion diseases and other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. In neurodegenerative diseases, nasal swab tests are currently being explored using seed amplification assay (SAA) of pathogenic misfolded proteins, such as prion, α-synuclein, and tau. These misfolded proteins can serve as templates for the conformational change of other copies from the native form into the same misfolded form in a prion-like manner. SAA for misfolded prion-like proteins from nasal swab extracts has been developed, conceptually analogous to PCR, showing high sensitivity and specificity for molecular diagnosis of degenerative diseases even in the prodromal stage. Cyclic amplification assay of nasal swab extracts is an attractive and feasible method for accurate and non-invasive detection of trace amount of pathogenic substances for screening and diagnosis of neurodegenerative disease.

[Clinical analysis of 31 patients with sinonasal neuroendocrine carcinoma].

Objective:To investigate the characteristics and prognostic factors of sinonasal neuroendocrine carcinoma （SNEC）. Methods:The clinical data of 31 patients with SNEC were retrospectively analyzed. Among the 31 patients, 3 cases were simply surgically removed, 4 cases were surgery + radiotherapy, 4 cases were surgery + chemotherapy, 10 cases were surgery + chemoradiotherapy, and 10 cases were simply given chemoradiotherapy without surgery. The study follow-up 8-64 months. Results:By the end of follow-up, 2 patients were lost to follow-up, 17 died, 12 survival, 8 relapsed and 5-year survival rate was 36.4％. High TNM stage, lymph node metastasis, skull base infiltration and Ki-67≥55％ were the negative prognostic factors for survival. Conclusion:SNEC is a rare aggressive tumor, with poor prognosis, high local recurrence rate, metastasis tendency, hidden disease. The comprehensive treatment of surgery combined with chemoradiotherapy is still the best treatment.

Long non-coding RNA LINC00346 contributes to cisplatin resistance in nasopharyngeal carcinoma by repressing miR-342-5p.

Cisplatin has been used as the first-line chemotherapy to treat advanced nasopharyngeal carcinoma (NPC), while acquired cisplatin resistance resulting from epigenetic regulation is not well understood. The relative expression of LINC00346 was detected in healthy persons, cisplatin-sensitive (CS) patients and cisplatin-resistant (CR) patients. The regulatory effect of LINC00346 on the proliferation was detected by cell-counting kit-8. Apoptosis was assayed by histone/DNA ELISA and Caspase-3 activity. Clonal formation and cisplatin resistance were also deciphered. Luciferase reporter and RNA immunoprecipitation assay were adopted to study the interaction between LINC00346 and miR-342-5p. LINC00346 was highly expressed in NPC patients, especially in CR patients, which was associated with cisplatin resistance and poor prognosis. Inhibition of LINC00346 expression promoted cisplatin sensitivity of NPC cells, while LINC00346 over-expression promoted cisplatin resistance of NPC cells. miR-342-5p expression was negatively correlated with cisplatin resistance, and microRNA-342-5p siRNAs treatment could rescue the cisplatin resistance diminished by LINC00346 inhibition. It was further found that miR-342-5p was negatively regulated by LINC00346. In conclusion, LINC00346 regulates the cisplatin resistance of NPC cells by inhibiting miR-342-5p, which could provide a potential target for chemotherapy resistance.

[Clinical analysis of 35 cases of adult rhabdomyosarcoma of nasal cavity and sinuses].

Objective:To investigate the clinical characteristics and prognostic factors of adult rhabdomyosarcoma（RMS） of nasal cavity and sinus. Method:There were 35 adult patients with RMS, including 22 with embryonal type and 13 with acinar type. Surgery + chemoradiotherapy（17 cases）, surgery + radiotherapy（6 cases）, surgery + chemotherapy（7 cases）（4 cases of seed implantation after surgery and chemotherapy）; Five patients were treated with antitumor drugs instead of surgery. Result:The study follow-up 9-62 months, adult nasal sinuses RMS total 5 years survival rate was 2.9%, among them the IRS stage>Ⅱ period, the infiltration of the skull base tumor, local lymph node metastasis, tumor diameter of 5 cm or more, 50% or higher Ki-67 are poor prognosis factor. Conclusion:RMS in nasal cavity and sinus are mostly embryonal type in adults, and the 5-year overall survival rate is low, which is related to larger primary tumor volume, local lymph node metastasis, skull base infiltration and higher ki-67 ratio at the first diagnosis in adults.

Upregulation of lncRNA H19 promotes nasopharyngeal carcinoma proliferation and metastasis in let-7 dependent manner.

The aim of this study is to analyse the expression status of long non-coding RNA (lncRNA) H19 in nasopharyngeal carcinoma and to unravel its oncogenic properties at molecular level. The abundance of H19, let-7a, b, g, i and HRAS was quantified by real-time PCR. Cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cell proliferation was evaluated by the cell counting. Cell migration and cell invasion were determined using transwell chamber and scattering colony formation. Tumour progression was monitored in xenograft tumour model and tail vein injection was adopted for lung metastasis assessment. Luciferase reporter assay was employed to interrogate the potential regulatory action of let-7 genes on H19 expression. The endogenous HRAS protein was quantified by western blotting. H19 was aberrantly over-expression in nasopharyngeal carcinoma, which intimately associated with poorer prognosis. H19-deficency significantly inhibited cell viability and suppressed cell proliferation. Furthermore, both migrative and invasive capacity were compromised by H19 knockdown. H19-silencing remarkably delayed xenograft tumour progression and lung metastasis. Mechanistically, H19 competitively sponged let-7 genes and therefore up-regulated HRAS, which consequently contributed to its oncogenic activity in nasopharyngeal carcinomas. Our study uncovered the oncogenic properties of H19 in nasopharyngeal carcinoma and highlighted the H19-let-7-HRAS signalling axis underlying the incidence and metastasis of this disease.

MiR-146a mimic attenuates murine allergic rhinitis by downregulating TLR4/TRAF6/NF-κB pathway.

Aim: This study aims to investigate whether microRNA (miR)-146a exerts therapeutic potential to allergic rhinitis (AR). Methods: Female BALB/c mice were randomly divided into the AR and miR-146a groups. miR-146a was administered into the nostril before ovalbumin (OVA) challenge daily on days 21-28. Results: The expression level of miR-146a in AR nasal mucosa was significantly decreased. miR-146a mimic markedly attenuated sneezing and nasal rubbing events, decreased the levels of ovalbumin-specific IgE as well as mastocyte- and basophil-related inflammatory cytokines, reduced inflammatory cells, affected the T-helper 2-released cytokines. Furthermore, miR-146a mimic inhibited the expressions of proteins relevant to Toll-like receptor 4 (TLR4)/TRAF6/NF-κB signaling pathway. Conclusion: The anti-inflammatory effects of miR-146a on AR might exert through the inhibition of the toll-like receptor 4 (TLR4)/TRAF6/NF-κB signaling pathway to some extent.