Esophageal squamous cell carcinoma (ESCC) is notorious for the rapid progression especially early tumor metastasis due to the unclear mechanism. Recently, ETV5 attracts much attention for its potential role as an oncogenic transcription factor involved in multiple cancers. However, no one reported the mechanism behind the association between ETV5 expression and esophageal squamous cell carcinoma progression. In this study, we found that ETV5 was upregulated in ESCC both from online database and our ESCC tissues and ETV5 was associated with tumor staging and prognosis. Knockdown of ETV5 or its downstream genes SKA1 and TRPV2 significantly suppress ESCC cells migration and invasion, respectively. Additionally, in vivo study showed knockdown of ETV5 inhibited tumor metastasis. Further experiments unveiled ETV5 could transcriptionally upregulate the expression of SKA1 and TRPV2 and further activate MMPs in ESCC progression. In conclusion, ETV5 was associated with ESCC tumor staging and ESCC prognosis clinically. ETV5 promoted metastasis of ESCC by activating MMPs through augmenting the transcription of SKA1 and TRPV2. ETV5 was likely to be a novel oncogene and therapeutic target in ESCC.
Purpose Thyroid function variation within thyroxine reference range has negative metabolic effects. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed definition. We aim to explore the effects of thyroid function status on prevalence and mortality of MAFLD. Methods Data of 10,666 participants from the Third National Health and Nutrition Examination Survey (NHANES III) were used. MAFLD was diagnosed based on the new definition. Thyroid function variation within thyroxine reference range was defined based on thyroid stimulating hormone (TSH) levels as following: subclinical hyperthyroidism, < 0.39 mIU/L; strict-normal thyroid function, 0.39–2.5 mIU/L; and low thyroid function, > 2.5 mIU/L, which was the combination of low-normal thyroid function (2.5–4.5 mIU/L) and subclinical hypothyroidism (> 4.5 mIU/L). Logistic and cox regression were used in multivariate analysis. Results Low thyroid function is independently associated with MAFLD (Odds ratio: 1.27). Compared with strict-normal thyroid function, subclinical hypothyroidism was significantly associated with increased risk for all-cause and cardiovascular mortality in total population (Hazard ratio [HR] for all-cause: 1.23; cardiovascular: 1.65) and MAFLD population (HR for all-cause: 1.32; cardiovascular: 1.99), meanwhile, with low-normal thyroid function group, increasing trend in mortality risk was observed. Furthermore, low thyroid function also showed significant negative impact on mortality in total and MAFLD population. Among thyroid function spectrum, mild subclinical hypothyroidism showed the highest HRs on mortality. Conclusions Low thyroid function is independent risk factor of MAFLD and is associated with increased risk for all-cause and cardiovascular mortality in MAFLD population. Reevaluation of TSH reference range should be considered.
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