The expression levels of MIR375 and MIR451a genes in subacute thyroiditis

Yıl 2024, Cilt: 49 Sayı: 2, 260 – 267, 30.06.2024

Mustafa Koçak , Nevin Karakuş , Merve Çatak

https://doi.org/10.17826/cumj.1379775

Öz

Amaç: Tiroid ağrısının en tipik nedeni subakut tiroidittir (SAT). SAT prevalansı kadınlarda erkeklere göre daha yüksektir ve yıllık ortalama sıklığı 100.000 kişide 12,1’dir. Mikro RNA’lar (miRNA’lar) adı verilen endojen, kısa, tek sarmallı, kodlamayan RNA’lar, gen ekspresyonunun inhibitörleridir. miRNA’lar gen ifadesinin transkripsiyon sonrası düzenlenmesinde önemlidir. Bu çalışmada, dolaşımdaki iki miRNA’nın (MIR451A ve MIR375) SAT’ın tespiti ve izlenmesinde belirteç olarak potansiyel faydasını araştırdık.
Gereç ve Yöntem: Bu çalışmaya 50 SAT hastası ve 41 sağlıklı birey dahil edildi. miRNA ekspresyon seviyeleri, kantitatif gerçek zamanlı polimeraz zincir reaksiyonu (qRT-PCR) yaklaşımı kullanılarak değerlendirildi. miRNA ifade düzeylerinin hesaplamak için 2-ΔΔCt tekniği kullanıldı. miRNA ifadesinin istatistiksel önemini değerlendirmek için t testi kullanıldı.
Bulgular: Sağlıklı kontroller ve SAT hastaları arasında MIR451A ekspresyon düzeyleri farklılık gösterirken, MIR375-3p ekspresyon düzeylerinin iki grupta da benzer olduğu belirlendi. MIR375-3p ve MIR451A ekspresyon düzeylerinin, farklı SAT evrelerinde (hipertiroid, ötiroid ve hipotiroid) benzer olduğu görüldü. MIR375-3p ve MIR451A’nın ekspresyon seviyeleri, SAT hastalarının klinik özellikleriyle ilişki açısından analiz edildi, ancak herhangi bir korelasyona rastlanmadı.
Sonuç: Bu çalışmada dolaşımdaki MIR451A’nın ekspresyon düzeyinin SAT hastalarında daha düşük olduğu bulundu, bu da MIR451A’nın SAT hastalığının başlangıcında etkili olabileceğini göstermektedir.

Anahtar Kelimeler

ekspresyon düzeyi, subakut tiroidit, MIR451A, MIR375.

Etik Beyan

Etik Kurulumuzun 20.02.2018 tarihli toplantısında görüşülen 18-KAEK-048 kayıt numaralı ''Subakut Tiroidit Hastalığında miRNA'ların Rolü'' başlıklı çalışmanız gerekçe, amaç, yaklaşım ve yöntemleri dikkate alınarak incelenmiş ve uygun bulunmuş olup, çalışmanın başvuru dosyasında belirtilen merkezde gerçekleştirilmesinde etik ve bilimsel sakınca bulunmadığına karar verilmiştir. Bilgilerinizi rica ederim.

Destekleyen Kurum

TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ TIP FAKÜLTESİ DEKANLIĞI KLİNİK ARAŞTIRMALAR ETİK KURUL KARARI

Proje Numarası

18-KAEK-048

Kaynakça

• Volpé R, Row VV, Ezrin C. Circulating viral and thyroid antibodies in subacute thyroiditis. J Clin Endocrinol Metab. 1967;27:1275–84.
• Bindra A, Braunstein GD. Thyroiditis. Am Fam Physician. 2006;73:1769–76.
• Hennessey JV. Subacute thyroiditis. 2000;Endotext.
• Fatourechi V, Aniszewski JP, Fatourechi GZE, Atkinson EJ, Jacobsen SJ. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J Clin Endocrinol Metab. 2003;88:2100–5.
• Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW. Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab. 2009;94:1853–78.
• Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA. 2003;100:9779–84.
• Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.
• Panwar B, Omenn GS, Guan Y. miRmine: a database of human miRNA expression profiles. Bioinformatics (Oxford, England). 2017;33:1554–60.
• Liu R, Ma X, Xu L, Wang D,J iang X, Zhu W et al. Differential MicroRNA expression in peripheral blood mononuclear cells from Graves’ disease patients. J Clin Endocrinol Metab. 2012;97:e968– 72.
• O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10:111–22.
• Yan JW,Lin JS,He XX. The emerging role of miR-375 in cancer. Int J Cancer. 2014;135:1011–8.
• Yang X, Nanayakkara J, Claypool D, Saghafinia S, Wong JJM, Xu M et al. A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells. Sci Rep. 2021;11:10455.
• Gan TQ, Chen WJ, Qin H, Huang SN, Yang LH, Fang YY et al. Clinical value and prospective pathway signaling of microrna-375 in lung adenocarcinoma: a study based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and bioinformatics analysis. Med Sci Monit . 2017;23:2453–64.
• Liu Y, Wang Q, Wen J, Wu Y, Man C. MiR-375: A novel multifunctional regulator. Life Sci. 2021;275:119323.
• Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C et al. Distribution of miRNA expression across human tissues. Nucleic Acids Res. 2016;44:3865–77.
• Liu SY, Deng SY, He Y Bin, Ni GX.miR-451 inhibits cell growth, migration and angiogenesis in human osteosarcoma via down-regulating IL 6R. Biochem Biophys Res Commun. 2017;482:987–93.
• Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26:1343–421.
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25:402–8.
• Lee RC, Feinbaum RL, Ambros V.The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.
• Pillai RS.MicroRNA function: Multiple mechanisms for a tiny RNA? RNA. 2005;11:1753–61.
• Dong H, Paquette M, Williams A, Thomas Zoeller R, Wade M, Yauk C. Thyroid hormone may regulate mRNA abundance in liver by acting on microRNAs. PloS One. 2010;5:e12136.
• Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. MicroRNA Expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008;93:1600–8.
• He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S et al. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA. 2005;102:19075–80.
• Karakus N, Catak M, Kutluturk F, Kocak M, Akman Ekici M, Citir M. The effects of circulating MIR22-3p and MIR16-1-3p levels in different stages of subacute thyroiditis. Nucleosides Nucleotides Nucleic Acids. 2023;42:436-47.
• Li H, Zhang X, Gao L, Min J, Zhang Y, Zhang R et al. TNF-alpha is upregulated in subacute thyroiditis and stimulates expression of miR-155-5p in thyroid follicle cells. Discov Med. 2018;26:67–77.
• Yamada H, Itoh M, Hiratsuka I, Hashimoto S. Circulating microRNAs in autoimmune thyroid diseases. Clin Endocrinol(Oxf). 2014;81:276–81.
• De La Chapelle A, Jazdzewski K. MicroRNAs in thyroid cancer. J Clin Endocrinol Metab. 2011;96:3326–36.
• Zhang D, Li Y, Liu S, Wang Ycheng, Guo F, Zhai Q et al.microRNA and thyroid hormone signaling in cardiac and skeletal muscle.Cell Biosci. 2017;7:14.
• Takakura S, Mitsutake N, Nakashima M, Namba H, Saenko VA, Rogounovitch TI et al. Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Sci. 2008;99:1147–54.
• Alfadda AA, Sallam RM, Elawad GE, Aldhukair H, Alyahya MM.Subacute thyroiditis: clinical presentation and long term outcome. Int J Endocrinol. 2014;2014:794-943.

The expression levels of MIR375 and MIR451a genes in subacute thyroiditis

Yıl 2024, Cilt: 49 Sayı: 2, 260 – 267, 30.06.2024

Mustafa Koçak , Nevin Karakuş , Merve Çatak

https://doi.org/10.17826/cumj.1379775

Öz

Purpose: The most typical reason for thyroid pain is subacute thyroiditis (SAT). Incidence of SAT is higher in women than in men and the average annual frequency of SAT is 12.1 cases per 100,000 people. Endogenous, brief, single-stranded non-coding RNAs, called micro RNAs (miRNAs), are inhibitors of gene expression. In the posttranscriptional regulation of gene expression, miRNAs are essential. In this investigation, we explored the potential utility of two circulating miRNAs, MIR451A and MIR375, as markers for the detection and monitoring of SAT.
Materials and Methods: Fifty SAT patients and 41 healthy people were enrolled in this study. Using the quantitative real-time polymerase chain reaction (qRT-PCR) approach, miRNA expression levels were assessed. The 2-ΔΔCt technique was used to calculate miRNA expression levels. The t-test was used to assess the statistical significance of miRNA expression.
Results: While MIR451A expression levels were discovered to vary between healthy controls and SAT patients, MIR375-3p expression levels were discovered to be similar in both groups. MIR375-3p and MIR451A expression levels were shown to be similarly in different SAT stages (hyperthyroid, euthyroid, and hypothyroid). The expression levels of MIR375-3p and MIR451A were analyzed for association with the clinical characteristics of SAT patients, but no correlation was observed.
Conclusion: In this study, it was found that the expression level of circulating MIR451A was lower in SAT patients, which shows that MIR451A might be effective in the SAT disease’s onset.

Anahtar Kelimeler

expression level, subacute thyroiditis, MIR451A, MIR375

Proje Numarası

18-KAEK-048

Kaynakça

• Volpé R, Row VV, Ezrin C. Circulating viral and thyroid antibodies in subacute thyroiditis. J Clin Endocrinol Metab. 1967;27:1275–84.
• Bindra A, Braunstein GD. Thyroiditis. Am Fam Physician. 2006;73:1769–76.
• Hennessey JV. Subacute thyroiditis. 2000;Endotext.
• Fatourechi V, Aniszewski JP, Fatourechi GZE, Atkinson EJ, Jacobsen SJ. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J Clin Endocrinol Metab. 2003;88:2100–5.
• Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW. Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab. 2009;94:1853–78.
• Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA. 2003;100:9779–84.
• Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.
• Panwar B, Omenn GS, Guan Y. miRmine: a database of human miRNA expression profiles. Bioinformatics (Oxford, England). 2017;33:1554–60.
• Liu R, Ma X, Xu L, Wang D,J iang X, Zhu W et al. Differential MicroRNA expression in peripheral blood mononuclear cells from Graves’ disease patients. J Clin Endocrinol Metab. 2012;97:e968– 72.
• O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10:111–22.
• Yan JW,Lin JS,He XX. The emerging role of miR-375 in cancer. Int J Cancer. 2014;135:1011–8.
• Yang X, Nanayakkara J, Claypool D, Saghafinia S, Wong JJM, Xu M et al. A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells. Sci Rep. 2021;11:10455.
• Gan TQ, Chen WJ, Qin H, Huang SN, Yang LH, Fang YY et al. Clinical value and prospective pathway signaling of microrna-375 in lung adenocarcinoma: a study based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and bioinformatics analysis. Med Sci Monit . 2017;23:2453–64.
• Liu Y, Wang Q, Wen J, Wu Y, Man C. MiR-375: A novel multifunctional regulator. Life Sci. 2021;275:119323.
• Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C et al. Distribution of miRNA expression across human tissues. Nucleic Acids Res. 2016;44:3865–77.
• Liu SY, Deng SY, He Y Bin, Ni GX.miR-451 inhibits cell growth, migration and angiogenesis in human osteosarcoma via down-regulating IL 6R. Biochem Biophys Res Commun. 2017;482:987–93.
• Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26:1343–421.
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25:402–8.
• Lee RC, Feinbaum RL, Ambros V.The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.
• Pillai RS.MicroRNA function: Multiple mechanisms for a tiny RNA? RNA. 2005;11:1753–61.
• Dong H, Paquette M, Williams A, Thomas Zoeller R, Wade M, Yauk C. Thyroid hormone may regulate mRNA abundance in liver by acting on microRNAs. PloS One. 2010;5:e12136.
• Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. MicroRNA Expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008;93:1600–8.
• He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S et al. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA. 2005;102:19075–80.
• Karakus N, Catak M, Kutluturk F, Kocak M, Akman Ekici M, Citir M. The effects of circulating MIR22-3p and MIR16-1-3p levels in different stages of subacute thyroiditis. Nucleosides Nucleotides Nucleic Acids. 2023;42:436-47.
• Li H, Zhang X, Gao L, Min J, Zhang Y, Zhang R et al. TNF-alpha is upregulated in subacute thyroiditis and stimulates expression of miR-155-5p in thyroid follicle cells. Discov Med. 2018;26:67–77.
• Yamada H, Itoh M, Hiratsuka I, Hashimoto S. Circulating microRNAs in autoimmune thyroid diseases. Clin Endocrinol(Oxf). 2014;81:276–81.
• De La Chapelle A, Jazdzewski K. MicroRNAs in thyroid cancer. J Clin Endocrinol Metab. 2011;96:3326–36.
• Zhang D, Li Y, Liu S, Wang Ycheng, Guo F, Zhai Q et al.microRNA and thyroid hormone signaling in cardiac and skeletal muscle.Cell Biosci. 2017;7:14.
• Takakura S, Mitsutake N, Nakashima M, Namba H, Saenko VA, Rogounovitch TI et al. Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Sci. 2008;99:1147–54.
• Alfadda AA, Sallam RM, Elawad GE, Aldhukair H, Alyahya MM.Subacute thyroiditis: clinical presentation and long term outcome. Int J Endocrinol. 2014;2014:794-943.

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