ABSTRACT
AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.
ABSTRACT
Objective:To study the value of CT texture analysis (CTTA) parameters in differential diagnosis of benign and malignant thyroid nodules in Hashimoto’s thyroiditis.Methods:From May. 2020 to Oct. 2021, 110 patients with thyroid nodules in the background of Hashimoto’s thyroiditis in the Radiology Department of Nanjing Integrated Hospital of Traditional Chinese and Western Medicine were selected, and CTTA was performed. CTTA parameters (entropy value, peak state and skewness) were counted. The pathological diagnosis results were taken as the "gold standard". Statistical pathological examination results were used to compare the general clinical characteristics and CTTA parameters of benign and malignant thyroid nodules. The receiver operating characteristic (ROC) was used to analyze the diagnostic value of CTTA parameters for thyroid nodules.Results:According to the clinicopathological examination, 43 of 110 patients with Hashimoto’s thyroiditis were malignant, accounting for 39.09%. Among them, 22 were papillary carcinoma, 13 were follicular carcinoma, 6 were medullary carcinoma, and 2 were malignant lymphoma; 67 cases were benign, accounting for 60.91%, including 32 nodular goiters, 20 Hashimoto’s nodules, 8 thyroid adenomas, and 7 focal inflammation. The levels of TSH, irregular shape, blurry border and calcification in patients with malignant thyroid nodules were higher than those in patients with benign thyroid nodules ( t/ χ2=13.167, 18.364, 20.180,17.621, P<0.001). In the background of Hashimoto’s thyroiditis, there was no significant difference in the peak and skewness of CTTA parameters between benign and malignant thyroid nodules ( t=1.633, 1.382, P=0.105, 0.170). The entropy value of patients with malignant thyroid nodules was higher than that of patients with benign thyroid nodules, and the difference was statistically significant ( t=9.862, P<0.001). ROC analysis showed that the cut-off value of entropy value for diagnosing benign and malignant thyroid nodules was 6.28, AUC value was 0.909, 95% CI was 0.839-0.955, sensitivity was 86.05% (37/43), and specificity was 88.06% (69/67) . Conclusion:CTTA parameters in Hashimoto’s thyroiditis patients with benign and malignant thyroid nodules are different, and CTTA parameters have certain diagnostic value for benign and malignant thyroid nodules.