Study On The Relationship Between Thyroid Nodules And Obesity And The Expression Of LncRNA In Papillary Thyroid Carcinoma

Objective: The association between thyroid nodules and adiposity remains controversial.We performed a cross-sectional,community-based study to examine whether thyroid nodules are associated with overweight and obesity,as defined with body mass index(BMI)and waist circumference.Methods: The study included 1482 subjects(≥ 20 years of age;residing in Nanjing,China)receiving questionnaire interview,anthropometric measurements,laboratory tests and thyroid ultrasonography in 2009–2010.Overweight and obesity were defined as BMI ≥ 24 and ≥ 28 kg/m~2,respectively.Central obesity was defined as waist circumference at ≥ 90 cm in men and ≥ 80 cm in women.A sensitivity analysis was conducted using the American Diabetes Association(ADA)criteria for overweight and obesity(BMI ≥ 23 and ≥25 kg/m~2).Results:(1)Thyroid nodules were identified in 12.6% of the subjects.A greater proportion of the subjects with thyroid nodules had a BMI at ≥24 kg/m~2(51.9% vs.40.5% in those without thyroid nodules,P = 0.003)and central obesity(43.3% vs.24.2%,P < 0.001).(2)After adjustment for other confounders,central obesity was still associated with significantly elevated risk of thyroid nodules(OR 1.62,95%CI 1.14–2.28),whereas obesity/overweight based on BMI was not in both the main analysis and sensitivity analysis with the alternative criteria.(3)In the subgroup analysis,BMI ≥24 kg/m~2(OR 1.61,95%CI 1.01–2.54),as well as BMI ≥25 kg/m~2(OR 1.95,95%CI 1.14–3.34),was significantly associated with higher risk of thyroid nodules among women.Using the ADA criteria,overweight and obesity were associated with thyroid nodules(OR 5.59,95%CI 1.39–22.51 and 5.15,95%CI 1.30–20.37)in thyroid-stimulating hormone(TSH)> 4.2 m IU/L subgroup.(4)Central obesity correlated with higher risk of thyroid nodules regardless of age(< 50 years: OR 1.87,95%CI 1.05–3.32;≥50 years: OR 1.54,95%CI 1.00–2.37)and in the following subgroups: men(OR 1.91,95%CI 1.14–3.20),TSH > 4.2 m IU/L(OR 3.05,95%CI 1.01–9.22),and urine iodine ≥200 μg/L(OR 1.79,95%CI 1.14–2.81).Conclusions: Waist circumference is more suitable than BMI for assessing risk of thyroid nodules in Chinese subjects.Objective:Papillary thyroid cancer(PTC)is the most frequent type of thyroid malignancy.In this study,we investigated the mechanisms whereby long non-coding RNAs(lnc RNAs)are associated with PTC pathogenesis.Methods: A lnc RNA microarray was performed to determine which lnc RNAs are differentially expressed in four paired PTC tissues relative to normal thyroid controls,and q RT-PCR was used for validation analysis to top 10 differentially expressed lnc RNAs in 86 PTC cases.A novel lnc RNA ENST00000539653.1(ENS-653)was examined to explore the correlation between its expression and clinicopathological parameters.Small interfering RNA(si RNA)transfection was then used in order to down-regulate ENS-653 expression in IHH4 PTC cells.Colony formation and CCK-8 assays were performed to assess the role of ENS-653 on the proliferation.The effect of ENS-653 on cell cycle and apoptosis of IHH4 cells was also observed,as well as western blot for relevant protein expression.It was also evaluated that how down-regulation of ENS-653 affected the mitogen-activated protein kinase(MAPK)signaling.Results:(1)The lnc RNA microarray exhibited 1878 differentially expressed lnc RNAs upon comparison with matched control samples(fold change ≥ 2.0,P < 0.05),of which 429 were upregulated and 1449 were downregulated.(2)ENST00000539653.1(ENS-653),one of the top 10 hits in this microarray,was selected for further analysis in 86 PTC cases.ENS-653 was expressed at higher levels in PTC tissue samples relative to controls,positively correlating both with tumor size and TNM stage.(3)In vitro,ENS-653 downregulation reduced the proliferation of IHH4 cells and led to G1-S phase arrest of the cell cycle,but had no impact on apoptosis.The expression of proliferation/cell cycle/apotosis – relevant proteins(PCNA、cyclin D1 and cleaved caspase-3)was also detected with relative changes.(4)ENS-653 downregulation also inactivated p-ERK1/2 and p-ERK5,but had no effect on p-JNK and p-p38.Further cell treatment with inhibitor U0126 of MAPK enhanced this effect on p-JNK and p-p38.Conclusions: ENS-653 exhibits oncogenic properties in PTC,and could be a diagnostic and/or prognostic PTC biomarker,in addition to possibly being a future target for therapy.