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Laringeal Skuamöz Hücreli Karsinomlu Hastalarda UCA1/miR-138/CDK6 Ağının Değerlendirilmesi

Yıl 2024, Cilt: 34 Sayı: 5, 666 - 670, 31.10.2024
https://doi.org/10.54005/geneltip.1493371

Öz

Amaç: Kodlamayan RNA’lar (ncRNA’lar), birçok kanser türünde tanı ve tedavi hedefi olma potansiyeline sahiptir. miRNA – mRNA ceRNA (yarışmalı endojen RNA) ağı son yıllarda üzerinde çalışılan ilginç bir konu olmuştur. Bu çalışmayla UCA1/miR-138/CDK6 ağının laringeal skuamöz hücreli karsinom (LSCC) ile ilişkisini araştırmayı amaçladık.
Gereç ve Yöntem: LSCC tanısı alan hastaların kanserli dokuları ve kontrol olarak da komşu normal doku örneklerinden çalışma yapıldı. Örneklerden RNA izolasyonu yapıldıktan sonra kantitatif gerçek zamanlı PCR (qRT-PCR) yöntemi ile UCA1, miR-138 ve CDK6 ekspresyonları değerlendirildi.
Bulgular: Kanserli ve kontrol doku örneklerinin ekspresyonları karşılaştırıldı. Kanser dokularında, istatistiksel olarak anlamlı olmamakla birlikte CDK6 ve UCA1 ekspresyonunun arttığı, miR-138 ekspresyonun ise azaldığı belirlendi.
Sonuç: Çalışmamız, bildiğimiz kadarıyla LSCC hastalarında UCA1/CDK6/miR-138 ağı ekspresyon profilinin çalışıldığı ilk çalışmadır. İstatistiksel olarak anlamlı sonuçlar elde edilememiş olmakla birlikte, sonuçlarımız UCA1, miR-138 ve CDK6 ağ çalışma literatürüyle benzerdi. Örnek sayısının daha fazla olduğu çalışmalar ve LSCC hücre dizileri ile yapılacak ileri çalışmalar, LSCC için tanı ve tedavi hedefi olabilecek bu yolağın fonksiyonlarını daha da netleştirecektir.

Proje Numarası

TTU- 2021-9277

Kaynakça

  • Kong X, Qi J, Yan Y, et al. Comprehensive analysis of differentially expressed profiles of lncRNAs, mRNAs, and miRNAs in laryngeal squamous cell carcinoma in order to construct a ceRNA network and identify potential biomarkers. J Cell Biochem. 2019;120(10):17963–74.
  • Zhang Q, Wang H, Zhao Q, et al. Evaluation of Risk Factors for Laryngeal Squamous Cell Carcinoma: A Single-Center Retrospective Study. Front Oncol. 2021;11(February).
  • Li H, Wang FL, Li W, et al. Aberrant expressed long non-coding RNAs in laryngeal squamous-cell carcinoma. Am J Otolaryngol - Head Neck Med Surg. 2019;40(5):615–25.
  • Liu H, Sun Y, Tian H, et al. Characterization of long non-coding RNA and messenger RNA profiles in laryngeal cancer by weighted gene co-expression network analysis. Aging (Albany NY). 2019;11(22):10074–99.
  • Aslantas M, Kilicaslan O, Eröz R,et al.. The Evaluation of the Genetic Variation Types of the Uridine Diphosphate Glucuronosyl Transferase 1A1 Gene by Next-Generation Sequencing and Their Effects on Bilirubin Levels in Obese Children. Genet Test Mol Biomarkers. 2024;28(7).
  • Doğan M, Eröz R, Tecellioğlu M, et al.. Clinical and Molecular Findings in a Turkish Family Who Had a (c.869- 1G>A) Splicing Variant in PSEN1 Gene with A Rare Condition: The Variant Alzheimer’s Disease with Spastic Paraparesis. Curr Alzheimer Res. 2022;19(3):223–35.
  • Arslanoğlu I, Eröz R, Yavuzyılmaz F, et al.. Variations In Monogenic Diabetes And Diabetes Susceptibility Genes In Pediatric Cases: Single Center Experience. Acta Endocrinol. 2023;19(4):512–22.
  • Acat M, Yıldız Gülhan P, Eröz R, et al.. Evaluation of both expression and serum protein levels of caspase-8 and mitogen-activated protein kinase 1 genes in patients with different severities of COVID-19 infection. Mol Biol Rep [Internet]. 2023;50(4):3241–8. Available from: https://doi.org/10.1007/s11033-023-08244-4
  • Tuşat M, Eroz R, Bölükbaş F, et al. Evaluation of the protective and therapeutic effects of extra virgin olive oil rich in phenol in experimental model of neonatal necrotizing enterocolitis by clinical disease score, ınflammation, apoptosis, and oxidative stress markers. Pediatr Surg Int [Internet]. 2024;40(1). Available from: https://doi.org/10.1007/s00383-024-05669-1
  • Karagun E, Eroz R. Argyrophilic nucleolar organizing regions in patients with Xeroderma Pigmentosum Group E. Exp Dermatol. 2021;30(3):416–7.
  • Damar İH, Eroz R. Argyrophilic Nucleolar Organizer Regions as New Biomarkers in ST-Elevation Myocardial Infarction. J Cardiovasc Dev Dis. 2022;9(2).
  • Shen Z, Li Q, Deng H, Lu D, et al.. Long non-coding RNA profiling in laryngeal squamous cell carcinoma and its clinical significance: Potential biomarkers for LSCC. PLoS One. 2014;9(9):1–9.
  • Cossu AM, Mosca L, Zappavigna S, , et al. Long non-coding RNAs as important biomarkers in laryngeal cancer and other head and neck tumours. Int J Mol Sci. 2019;20(14).
  • Shi Y, Yang D, Qin Y. Identifying prognostic lncRNAs based on a ceRNA regulatory network in laryngeal squamous cell carcinoma. BMC Cancer. 2021;21(1):1–15.
  • Lorenzi L, Avila Cobos F, Decock A, , et al. Long noncoding RNA expression profiling in cancer: Challenges and opportunities. Genes Chromosom Cancer. 2019;58(4):191–9.
  • Yeh M, Oh CS, Yoo JY, et al.. Pivotal role of microRNA-138 in human cancers. Am J Cancer Res [Internet]. 2019;9(6):1118–26. Available from:http://www.ncbi.nlm.nih.gov/pubmed/31285946%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6610051
  • Salmena L, Poliseno L, Tay Y, et al.. A ceRNA hypothesis: The rosetta stone of a hidden RNA language? Cell [Internet]. 2011;146(3):353–8. Available from: http://dx.doi.org/10.1016/j.cell.2011.07.014
  • Zhang Y, Xu Y, Feng L, et al. Comprehensive characterization of lncRNA-mRNA related ceRNA network across 12 major cancers. Oncotarget. 2016;7(39):64148–67.
  • Xuan W, Yu H, Zhang X, et al.. Crosstalk between the lncRNA UCA1 and microRNAs in cancer. FEBS Lett. 2019;593(15):1901–14.
  • Sun S, Gong C, Yuan K. LncRNA UCA1 promotes cell proliferation, invasion and migration of laryngeal squamous cell carcinoma cells by activating Wnt/β‑catenin signaling pathway. Exp Ther Med. 2018;1182–9.
  • Xun G, Ma M, Li B, et al.. miR-138 and miR-193 target long non-coding RNA UCA1 to inhibit cell proliferation, migration, and invasion of lung cancer. Thorac Cancer. 2020;11(9):2681–9.
  • Sun YD, Liu Q, Yang HX, et al. Long non-coding RNA UCA1 mediates proliferation and metastasis of laryngeal squamous cell carcinoma cells via regulating miR-185-5p/HOXA13 axis. Eur Rev Med Pharmacol Sci. 2021;25(3):1366–78.
  • Wang N, Wang L, Pan X. Long non-coding rna trpm2-as promotes cell migration and invasion by serving as a cerna of mir-138 and inducing sox4-mediated emt in laryngeal squamous cell carcinoma. Cancer Manag Res. 2020;12:7805–12.
  • Qiu S, Huang D, Yin D, et al. Suppression of tumorigenicity by MicroRNA-138 through inhibition of EZH2-CDK4/6-pRb-E2F1 signal loop in glioblastoma multiforme. Biochim Biophys Acta - Mol Basis Dis [Internet]. 2013;1832(10):1697–707. Available from: http://dx.doi.org/10.1016/j.bbadis.2013.05.015
  • Zhu Z, Tang J, Wang J, et al.. MIR-138 acts as a tumor suppressor by targeting EZH2 and enhances cisplatin-induced apoptosis in osteosarcoma cells. PLoS One. 2016;11(3):1–12.
  • Si F, Sun J, Wang C. MicroRNA-138 suppresses cell proliferation in laryngeal squamous cell carcinoma via inhibiting EZH2 and PI3K/AKT signaling. Exp Ther Med. 2017;14(3):1967–74.
  • Gao S, Wang J, Xie J, et al.. Role of miR-138 in the regulation of larynx carcinoma cell metastases. Tumor Biol [Internet]. 2016;37(12):15601–6. Available from: http://dx.doi.org/10.1007/s13277-015-4244-y
  • Poomsawat S, Sanguansin S, Punyasingh J, et al.Expression of cdk6 in head and neck squamous cell carcinoma. Clin Oral Investig. 2016;20(1):57–63.
  • Cui X, Yu T, Shang J, et al.. Long non-coding RNA CDKN2B-AS1 facilitates laryngeal squamous cell cancer through regulating miR-497/CDK6 pathway. Onco Targets Ther. 2019;12:8853–62.

Evaluation of UCA1/miR-138/CDK6 Network in the Patients with Laryngeal Squamous Cell Carcinoma

Yıl 2024, Cilt: 34 Sayı: 5, 666 - 670, 31.10.2024
https://doi.org/10.54005/geneltip.1493371

Öz

Objective: Noncoding RNAs (ncRNAs) have the potential to be diagnostic and therapeutic targets, in many cancer types. miRNA ‐ mRNA ceRNA (competing endogenous RNA) network in cancer has been an interesting topic that has been studied in recent years.
We aimed to investigate the relationship of UCA1/miR-138/CDK6 network with laryngeal squamous cell carcinoma (LSCC).
Material and Methods: We studied with the cancerous tissue and as the control; neighboring normal tissue samples of the patients with diagnosis of LSCC. UCA1, miR-138 and CDK6 expression analysis was made by quantitative real-time PCR (qRT-PCR) method after RNA isolation of the samples.
Results: Expressions of cancerous tissue samples and normal adjacent tissue samples as controls were compared. CDK6 and UCA1 levels were increased and miR-138 levels were found to be decreased in cancer tissues but not statistically significant.
Conclusions: To the best of our knowledge there is no study to provide an expression profile of the UCA1/CDK6/miR-138 network for LSCC patients. Although we could not obtain statistically significant results, our results were similar with the UCA1, miR‐138, and CDK6 axis literature. Further studies with larger patient samples and LSCC cell lines may confirm the function of this axis, which might be a diagnostic and therapeutic target for LSCC.

Etik Beyan

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of ??? University (B.30.2.???.0.01.00/60). Written informed consent was obtained from all participants.

Destekleyen Kurum

Ataturk University BAP coordinatory unit

Proje Numarası

TTU- 2021-9277

Kaynakça

  • Kong X, Qi J, Yan Y, et al. Comprehensive analysis of differentially expressed profiles of lncRNAs, mRNAs, and miRNAs in laryngeal squamous cell carcinoma in order to construct a ceRNA network and identify potential biomarkers. J Cell Biochem. 2019;120(10):17963–74.
  • Zhang Q, Wang H, Zhao Q, et al. Evaluation of Risk Factors for Laryngeal Squamous Cell Carcinoma: A Single-Center Retrospective Study. Front Oncol. 2021;11(February).
  • Li H, Wang FL, Li W, et al. Aberrant expressed long non-coding RNAs in laryngeal squamous-cell carcinoma. Am J Otolaryngol - Head Neck Med Surg. 2019;40(5):615–25.
  • Liu H, Sun Y, Tian H, et al. Characterization of long non-coding RNA and messenger RNA profiles in laryngeal cancer by weighted gene co-expression network analysis. Aging (Albany NY). 2019;11(22):10074–99.
  • Aslantas M, Kilicaslan O, Eröz R,et al.. The Evaluation of the Genetic Variation Types of the Uridine Diphosphate Glucuronosyl Transferase 1A1 Gene by Next-Generation Sequencing and Their Effects on Bilirubin Levels in Obese Children. Genet Test Mol Biomarkers. 2024;28(7).
  • Doğan M, Eröz R, Tecellioğlu M, et al.. Clinical and Molecular Findings in a Turkish Family Who Had a (c.869- 1G>A) Splicing Variant in PSEN1 Gene with A Rare Condition: The Variant Alzheimer’s Disease with Spastic Paraparesis. Curr Alzheimer Res. 2022;19(3):223–35.
  • Arslanoğlu I, Eröz R, Yavuzyılmaz F, et al.. Variations In Monogenic Diabetes And Diabetes Susceptibility Genes In Pediatric Cases: Single Center Experience. Acta Endocrinol. 2023;19(4):512–22.
  • Acat M, Yıldız Gülhan P, Eröz R, et al.. Evaluation of both expression and serum protein levels of caspase-8 and mitogen-activated protein kinase 1 genes in patients with different severities of COVID-19 infection. Mol Biol Rep [Internet]. 2023;50(4):3241–8. Available from: https://doi.org/10.1007/s11033-023-08244-4
  • Tuşat M, Eroz R, Bölükbaş F, et al. Evaluation of the protective and therapeutic effects of extra virgin olive oil rich in phenol in experimental model of neonatal necrotizing enterocolitis by clinical disease score, ınflammation, apoptosis, and oxidative stress markers. Pediatr Surg Int [Internet]. 2024;40(1). Available from: https://doi.org/10.1007/s00383-024-05669-1
  • Karagun E, Eroz R. Argyrophilic nucleolar organizing regions in patients with Xeroderma Pigmentosum Group E. Exp Dermatol. 2021;30(3):416–7.
  • Damar İH, Eroz R. Argyrophilic Nucleolar Organizer Regions as New Biomarkers in ST-Elevation Myocardial Infarction. J Cardiovasc Dev Dis. 2022;9(2).
  • Shen Z, Li Q, Deng H, Lu D, et al.. Long non-coding RNA profiling in laryngeal squamous cell carcinoma and its clinical significance: Potential biomarkers for LSCC. PLoS One. 2014;9(9):1–9.
  • Cossu AM, Mosca L, Zappavigna S, , et al. Long non-coding RNAs as important biomarkers in laryngeal cancer and other head and neck tumours. Int J Mol Sci. 2019;20(14).
  • Shi Y, Yang D, Qin Y. Identifying prognostic lncRNAs based on a ceRNA regulatory network in laryngeal squamous cell carcinoma. BMC Cancer. 2021;21(1):1–15.
  • Lorenzi L, Avila Cobos F, Decock A, , et al. Long noncoding RNA expression profiling in cancer: Challenges and opportunities. Genes Chromosom Cancer. 2019;58(4):191–9.
  • Yeh M, Oh CS, Yoo JY, et al.. Pivotal role of microRNA-138 in human cancers. Am J Cancer Res [Internet]. 2019;9(6):1118–26. Available from:http://www.ncbi.nlm.nih.gov/pubmed/31285946%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6610051
  • Salmena L, Poliseno L, Tay Y, et al.. A ceRNA hypothesis: The rosetta stone of a hidden RNA language? Cell [Internet]. 2011;146(3):353–8. Available from: http://dx.doi.org/10.1016/j.cell.2011.07.014
  • Zhang Y, Xu Y, Feng L, et al. Comprehensive characterization of lncRNA-mRNA related ceRNA network across 12 major cancers. Oncotarget. 2016;7(39):64148–67.
  • Xuan W, Yu H, Zhang X, et al.. Crosstalk between the lncRNA UCA1 and microRNAs in cancer. FEBS Lett. 2019;593(15):1901–14.
  • Sun S, Gong C, Yuan K. LncRNA UCA1 promotes cell proliferation, invasion and migration of laryngeal squamous cell carcinoma cells by activating Wnt/β‑catenin signaling pathway. Exp Ther Med. 2018;1182–9.
  • Xun G, Ma M, Li B, et al.. miR-138 and miR-193 target long non-coding RNA UCA1 to inhibit cell proliferation, migration, and invasion of lung cancer. Thorac Cancer. 2020;11(9):2681–9.
  • Sun YD, Liu Q, Yang HX, et al. Long non-coding RNA UCA1 mediates proliferation and metastasis of laryngeal squamous cell carcinoma cells via regulating miR-185-5p/HOXA13 axis. Eur Rev Med Pharmacol Sci. 2021;25(3):1366–78.
  • Wang N, Wang L, Pan X. Long non-coding rna trpm2-as promotes cell migration and invasion by serving as a cerna of mir-138 and inducing sox4-mediated emt in laryngeal squamous cell carcinoma. Cancer Manag Res. 2020;12:7805–12.
  • Qiu S, Huang D, Yin D, et al. Suppression of tumorigenicity by MicroRNA-138 through inhibition of EZH2-CDK4/6-pRb-E2F1 signal loop in glioblastoma multiforme. Biochim Biophys Acta - Mol Basis Dis [Internet]. 2013;1832(10):1697–707. Available from: http://dx.doi.org/10.1016/j.bbadis.2013.05.015
  • Zhu Z, Tang J, Wang J, et al.. MIR-138 acts as a tumor suppressor by targeting EZH2 and enhances cisplatin-induced apoptosis in osteosarcoma cells. PLoS One. 2016;11(3):1–12.
  • Si F, Sun J, Wang C. MicroRNA-138 suppresses cell proliferation in laryngeal squamous cell carcinoma via inhibiting EZH2 and PI3K/AKT signaling. Exp Ther Med. 2017;14(3):1967–74.
  • Gao S, Wang J, Xie J, et al.. Role of miR-138 in the regulation of larynx carcinoma cell metastases. Tumor Biol [Internet]. 2016;37(12):15601–6. Available from: http://dx.doi.org/10.1007/s13277-015-4244-y
  • Poomsawat S, Sanguansin S, Punyasingh J, et al.Expression of cdk6 in head and neck squamous cell carcinoma. Clin Oral Investig. 2016;20(1):57–63.
  • Cui X, Yu T, Shang J, et al.. Long non-coding RNA CDKN2B-AS1 facilitates laryngeal squamous cell cancer through regulating miR-497/CDK6 pathway. Onco Targets Ther. 2019;12:8853–62.
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İç Hastalıkları, Tıbbi Genetik (Kanser Genetiği hariç)
Bölüm Original Article
Yazarlar

Neslihan Cinkara 0000-0003-4869-0891

Çiğdem Yüce Kahraman 0000-0003-1957-9596

Arzu Tatar 0000-0002-4486-2695

Abdulgani Tatar 0000-0001-7273-1679

Proje Numarası TTU- 2021-9277
Erken Görünüm Tarihi 27 Ekim 2024
Yayımlanma Tarihi 31 Ekim 2024
Gönderilme Tarihi 31 Mayıs 2024
Kabul Tarihi 26 Ağustos 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 34 Sayı: 5

Kaynak Göster

Vancouver Cinkara N, Yüce Kahraman Ç, Tatar A, Tatar A. Evaluation of UCA1/miR-138/CDK6 Network in the Patients with Laryngeal Squamous Cell Carcinoma. Genel Tıp Derg. 2024;34(5):666-70.