A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression.

BACKGROUND: The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. METHODS: We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. RESULTS: Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. CONCLUSION: Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

Association of sudden sensorineural hearing loss with meteorological factors: a time series study in Hefei, China, and a literature review.

Air pollution can cause disease and has become a major global environmental problem. It is currently believed that air pollution may be related to the progression of SSNHL. As a rapidly developing city in recent years, Hefei has serious air pollution. In order to explore the correlation between meteorological variables and SSNHL admissions, we conducted this study. This study investigated the short-term associations between SSNHL patients admitted to the hospital and Hefei climatic variables. The daily data on SSNHL-related hospital admissions and meteorological variables containing mean temperature (T-mean; °C), diurnal temperature range (DTR; °C), atmospheric pressure (AP; Hp), and relative humidity (RH; %), from 2014 to 2021 (2558 days), were collected. A time-series analysis integrating distributed lag non-linear models and generalized linear models was used. PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Literature published up to August 2023 was reviewed to explore the potential impact mechanisms of meteorological factors on SSNHL. The mechanisms were determined in detail, focusing on wind speed, air pressure, temperature, humidity, and air pollutants. Using a median of 50.00% as a baseline, the effect of exceedingly low T-mean in the single-day hysteresis effect model began at a lag of 8 days (RR = 1.032, 95% CI: 1.001 ~ 1.064). High DTR affected the admission rate for SSNHL on lag 0 day. The significance of the effect was the greatest on that day (RR = 1.054, 95% CI: 1.007 ~ 1.104) and then gradually decreased. High and exceedingly high RH affected the admission rate SSNHL on lag 0 day, and these effects lasted for 8 and 7 days, respectively. There were significant associations between all grades of AP and SSNHL. This is the first study to assess the effect of meteorological variables on SSNHL-related admissions in China using a time-series approach. Long-term exposures to high DTR, RH values, low T-mean values, and all AP grades enhance the incidence of SSNHL in residents. Limiting exposure to extremes of ambient temperature and humidity may reduce the number of SSNHL-related hospital visits in the region. It is advisable to maintain a suitable living environment temperature and avoid extreme temperature fluctuations and high humidity. During periods of high air pollution, it is recommended to stay indoors and refrain from outdoor exercise.