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Elevated expression of let-7b-3p enhances aggressiveness of larynx squamous cell carcinoma cells

Yıl 2025, Cilt: 7 Sayı: 1, 27 - 32, 10.01.2025

Murat Kaya , Esra Güzel Tanoğlu , İlknur Süer , Ömer Faruk Karataş , Şükrü Öztürk , Mehmet Yılmaz , Kıvanç Çefle , Mustafa Özen

https://doi.org/10.38053/acmj.1579621

Öz

Aims: Larynx squamous cell carcinoma (LSCC) is the second most common head and neck malignancy. While let-7b-3p has been shown to have a role in cancer progression in malignancies, there is no research examining the association between LSCC and let-7b-3p. This study aimed to investigate the expression status of let-7b-3p and the potential roles of this microRNA (miRNA) in LSCC.
Methods: Using quantitative real-time polymerase chain reaction (qRT-PCR), we examined the expression status of let-7b3p in 36 LSCC samples and the neighboring normal tissues. Then, the let-7b-3p miRNA mimic was transfected into Hep-2 cells via lipofectamine 2000 reagents. Cell viability was determined using the cell viability detection (CVDK-8) kit, and cell migration was evaluated with the scratch assay. To identify differentially expressed genes (DEGs) in larynx cancer GSE137308 and GSE130605 datasets were downloaded and reanalyzed using Gene Expression Omnibus (GEO2R) tool. Potential target genes of let-7b-3p were investigated in the miRNA target prediction and functional annotation database (miRDB). Shared genes between geo datasets and miRDB results were identified and the relationship between these genes and LSCC was investigated in the literature.
Results: We demonstrated that the expression levels of let-7b-3p was significantly upregulated in LSCC tumor tissues in comparison to the corresponding normal tissues. Mimic let-7b-3p transfection enhanced Hep-2 cell proliferation and migration. In vitro and bioinformatics analysis showed that overexpression of let-7b-3p can enhance the larynx cancer cell proliferation and migration through MYBPC1.
Conclusion: It was evaluated that let-7b-3p/MYBPC1 axis could potentially affect the LSCC process. Let-7b-3p has the potential to be a biomarker for LSCC, therefore, the let-7b-3p/ MYBPC1/LSCC relationship should be elucidated with new studies.

Anahtar Kelimeler

Let-7b-3p larynx squamous cell carcinoma MYBPC1 bioinformatics

Etik Beyan

The Institutional Review Board of Istanbul-Cerrahpasa University, Cerrahpasa Faculty of Medicine, evaluated and approved the ethical considerations of the study (83045809/604.01/02-221477).

Destekleyen Kurum

This study was conducted using the doctoral thesis data of the corresponding author. The authors declared that this study has received no spesific financial support.

Teşekkür

We thanks to Istanbul-Cerrahpasa Medical Faculty, Department of Otolaryngology to providing tumor tissues.

Kaynakça

  • Liberale C, Soloperto D, Marchioni A, Monzani D, Sacchetto L. Updates on larynx cancer: risk factors and oncogenesis. Int J Mol Sci. 2023;24(16): 12913.
  • Erdoğan C, Kaya M, Suer İ. A bioinformatics analysis of circRNA/miRNA/mRNA interactions in acute myeloid leukemia. Experimed. 2023;13(1):45-53.
  • Kaya M. Bioinformatics evaluation of the circRNA–miRNA–mRNA axis in cervical squamous cell carcinoma. Explor Med. 2024;5(5):553-65.
  • Afonso-Grunz F, Müller S. Principles of miRNA-mRNA interactions: beyond sequence complementarity. Cell Mol Life Sci. 2015;72(16):3127-3141.
  • Kaya M, Abuaisha A, Süer İ, et al. Overexpression of CDC25A, AURKB, and TOP2A genes could be an important clue for luminal a breast cancer. Eur J Breast Health. 2024;20(4):284-291.
  • Suer I, Kaya M. Is the AURKB gene involved in aml cell proliferation since it is targeted by miR-34a-5p and let-7b-5p? Konuralp Med J. 2023; 15(1):16-23.
  • Bagatir G, Kaya M, Suer I, et al. The effect of Anzer honey on X-ray induced genotoxicity in human lymphocytes: an in vitro study. Microsc Res Tech. 2022;85(6):2241-2250.
  • Almeida MI, Nicoloso MS, Zeng L, et al. Strand-specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells. Gastroenterology. 2012;142(4):886-896.e9.
  • Kenyon JD, Sergeeva O, Somoza RA, et al. Analysis of -5p and -3p strands of miR-145 and miR-140 during mesenchymal stem cell chondrogenic differentiation. Tissue Eng Part A. 2019;25(1-2):80-90.
  • Ren LL, Yan TT, Shen CQ, et al. The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis. Cell Death Dis. 2018;9(6):687.
  • Huang Y, Liu Y, Huang J, et al. Let 7b 5p promotes cell apoptosis in Parkinson's disease by targeting HMGA2. Mol Med Rep. 2021;24(5):820.
  • Liu X, Zhao P, Du X, et al. Let-7b-5p promotes triptolide-induced growth-inhibiting effects in glioma by targeting IGF1R. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(8):5909-5925.
  • Dai Y, Liu J, Li X, et al. Let-7b-5p inhibits colon cancer progression by prohibiting APC ubiquitination degradation and the Wnt pathway by targeting NKD1. Cancer Sci. 2023;114(5):1882-1897.
  • Kaya M, Abuaisha A, Suer I, et al. Turmeric inhibits MDA-MB-231 cancer cell proliferation, altering miR-638-5p and its potential targets. Eur J Breast Health. 2024;20(2):102-109.
  • Erdogan C, Suer I, Kaya M, Ozturk S, Aydin N, Kurt Z. Bioinformatics analysis of the potentially functional circRNA-miRNA-mRNA network in breast cancer. PLoS One. 2024;19(4):e0301995.
  • Kaya M, Karataş ÖF. The relationship between larynx cancer and microRNAs. Van Med J. 2020;27(4):535-541.
  • Broseghini E, Filippini DM, Fabbri L, et al. Diagnostic and prognostic value of microRNAs in patients with laryngeal cancer: a systematic review. Noncoding RNA. 2023;9(1):9.
  • Broughton JP, Lovci MT, Huang JL, Yeo GW, Pasquinelli AE. Pairing beyond the seed supports microRNA targeting specificity. Mol Cell. 2016;64(2):320-333.
  • Zhang WT, Zhang GX, Gao SS. The potential diagnostic accuracy of let-7 family for cancer: a meta-analysis. Technol Cancer Res Treat. 2021;20:15330338211033061.
  • Ma Y, Shen N, Wicha MS, Luo M. The roles of the let-7 family of microRNAs in the regulation of cancer stemness. Cells. 2021;10(9):2415.
  • Li L, Zhang X, Lin Y, et al. Let-7b-5p inhibits breast cancer cell growth and metastasis via repression of hexokinase 2-mediated aerobic glycolysis. Cell Death Discov. 2023;9(1):114.
  • Bahojb Mahdavi SZ, Pouladi N, Amini M, et al. Let-7a-3p overexpression increases chemosensitivity to carmustine and synergistically promotes autophagy and suppresses cell survival in U87MG glioblastoma cancer cells. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(9):6903-6918.
  • Jiang J, Liu HL, Tao L, et al. Let 7d inhibits colorectal cancer cell proliferation through the CST1/p65 pathway. Int J Oncol. 2018;53(2):781-790.
  • Demirel G, Tanoglu EG, Aslıyuksek H. Evaluation of microRNA let-7b-3p expression levels in methamphetamine abuse. Rev Assoc Med Bras (1992). 2023;69(4):e20221391.
  • Dai R, Zhang L, Jin H, et al. Differential expression profile of urinary exosomal microRNAs in patients with mesangial proliferative glomerulonephritis. Aging (Albany NY). 2023;15(3):866-880.
  • Liu K, Ma L, Zhou F, et al. Identification of microRNAs related to myocardial ischemic reperfusion injury. J Cell Physiol. 2019;234(7): 11380-11390.
  • Chirshev E, Oberg KC, Ioffe YJ, Unternaehrer JJ. Let-7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer. Clin Transl Med. 2019;8(1):24.
  • Murray MJ, Bailey S, Raby KL, et al. Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma. Oncogenesis. 2014;3(2): e87.
  • Chen M, Xu R, Rai A, et al. Distinct shed microvesicle and exosome microRNA signatures reveal diagnostic markers for colorectal cancer. PLoS One. 2019;14(1):e0210003.
  • Weaver DT, Pishas KI, Williamson D, et al. Network potential identifies therapeutic miRNA cocktails in Ewing sarcoma. PLoS Comput Biol. 2021;17(10):e1008755.
  • Li Y, Dong R, Lu M, et al. Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma. Transl Lung Cancer Res. 2021;10(4):1841-1856.
  • Zhang B, Liu Y, Yu J, Lin X. Upregulation of FGF9 and NOVA1 in cancer-associated fibroblasts promotes cell proliferation, invasion and migration of triple negative breast cancer. Drug Dev Res. 2024;85(3): e22185.
  • Yotsumoto T, Maemura K, Watanabe K, et al. NRXN1 as a novel potential target of antibody-drug conjugates for small cell lung cancer. Oncotarget. 2020;11(39):3590-3600.
  • Li W, Zhou K, Li M, et al. Identification of SCN7A as the key gene associated with tumor mutation burden in gastric cancer. BMC Gastroenterol. 2022;22(1):45.
  • Ma Z, Li Z, Wang S, et al. ZMAT1 acts as a tumor suppressor in pancreatic ductal adenocarcinoma by inducing SIRT3/p53 signaling pathway. J Exp Clin Cancer Res. 2022;41(1):130.
  • Su N, Qiu H, Chen Y, Yang T, Yan Q, Wan X. miR-205 promotes tumor proliferation and invasion through targeting ESRRG in endometrial carcinoma. Oncol Rep. 2013;29(6):2297-2302.
  • Ha K, Buchan JG, Alvarado DM, et al. MYBPC1 mutations impair skeletal muscle function in zebrafish models of arthrogryposis. Hum Mol Genet. 2013;22(24):4967-4977.
  • Liu J, Song J, Li C. MYBPC1 is a key regulator for laryngeal carcinoma formation. Anticancer Drugs. 2023;34(1):1-8.
  • Zhang J, Jiang S, Gu D, et al. Identification of novel molecular subtypes and a signature to predict prognosis and therapeutic response based on cuproptosis-related genes in prostate cancer. Front Oncol. 2023;13: 1162653.
  • Pudova EA, Lukyanova EN, Nyushko KM, et al. Differentially expressed genes associated with prognosis in locally advanced lymph node-negative prostate cancer. Front Genet. 2019;10:730.
  • Hu H, Wang J, Gupta A, et al. RANKL expression in normal and malignant breast tissue responds to progesterone and is up-regulated during the luteal phase. Breast Cancer Res Treat. 2014;146(3):515-523.

Yıl 2025, Cilt: 7 Sayı: 1, 27 - 32, 10.01.2025

Murat Kaya , Esra Güzel Tanoğlu , İlknur Süer , Ömer Faruk Karataş , Şükrü Öztürk , Mehmet Yılmaz , Kıvanç Çefle , Mustafa Özen

https://doi.org/10.38053/acmj.1579621

Öz

Kaynakça

  • Liberale C, Soloperto D, Marchioni A, Monzani D, Sacchetto L. Updates on larynx cancer: risk factors and oncogenesis. Int J Mol Sci. 2023;24(16): 12913.
  • Erdoğan C, Kaya M, Suer İ. A bioinformatics analysis of circRNA/miRNA/mRNA interactions in acute myeloid leukemia. Experimed. 2023;13(1):45-53.
  • Kaya M. Bioinformatics evaluation of the circRNA–miRNA–mRNA axis in cervical squamous cell carcinoma. Explor Med. 2024;5(5):553-65.
  • Afonso-Grunz F, Müller S. Principles of miRNA-mRNA interactions: beyond sequence complementarity. Cell Mol Life Sci. 2015;72(16):3127-3141.
  • Kaya M, Abuaisha A, Süer İ, et al. Overexpression of CDC25A, AURKB, and TOP2A genes could be an important clue for luminal a breast cancer. Eur J Breast Health. 2024;20(4):284-291.
  • Suer I, Kaya M. Is the AURKB gene involved in aml cell proliferation since it is targeted by miR-34a-5p and let-7b-5p? Konuralp Med J. 2023; 15(1):16-23.
  • Bagatir G, Kaya M, Suer I, et al. The effect of Anzer honey on X-ray induced genotoxicity in human lymphocytes: an in vitro study. Microsc Res Tech. 2022;85(6):2241-2250.
  • Almeida MI, Nicoloso MS, Zeng L, et al. Strand-specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells. Gastroenterology. 2012;142(4):886-896.e9.
  • Kenyon JD, Sergeeva O, Somoza RA, et al. Analysis of -5p and -3p strands of miR-145 and miR-140 during mesenchymal stem cell chondrogenic differentiation. Tissue Eng Part A. 2019;25(1-2):80-90.
  • Ren LL, Yan TT, Shen CQ, et al. The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis. Cell Death Dis. 2018;9(6):687.
  • Huang Y, Liu Y, Huang J, et al. Let 7b 5p promotes cell apoptosis in Parkinson's disease by targeting HMGA2. Mol Med Rep. 2021;24(5):820.
  • Liu X, Zhao P, Du X, et al. Let-7b-5p promotes triptolide-induced growth-inhibiting effects in glioma by targeting IGF1R. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(8):5909-5925.
  • Dai Y, Liu J, Li X, et al. Let-7b-5p inhibits colon cancer progression by prohibiting APC ubiquitination degradation and the Wnt pathway by targeting NKD1. Cancer Sci. 2023;114(5):1882-1897.
  • Kaya M, Abuaisha A, Suer I, et al. Turmeric inhibits MDA-MB-231 cancer cell proliferation, altering miR-638-5p and its potential targets. Eur J Breast Health. 2024;20(2):102-109.
  • Erdogan C, Suer I, Kaya M, Ozturk S, Aydin N, Kurt Z. Bioinformatics analysis of the potentially functional circRNA-miRNA-mRNA network in breast cancer. PLoS One. 2024;19(4):e0301995.
  • Kaya M, Karataş ÖF. The relationship between larynx cancer and microRNAs. Van Med J. 2020;27(4):535-541.
  • Broseghini E, Filippini DM, Fabbri L, et al. Diagnostic and prognostic value of microRNAs in patients with laryngeal cancer: a systematic review. Noncoding RNA. 2023;9(1):9.
  • Broughton JP, Lovci MT, Huang JL, Yeo GW, Pasquinelli AE. Pairing beyond the seed supports microRNA targeting specificity. Mol Cell. 2016;64(2):320-333.
  • Zhang WT, Zhang GX, Gao SS. The potential diagnostic accuracy of let-7 family for cancer: a meta-analysis. Technol Cancer Res Treat. 2021;20:15330338211033061.
  • Ma Y, Shen N, Wicha MS, Luo M. The roles of the let-7 family of microRNAs in the regulation of cancer stemness. Cells. 2021;10(9):2415.
  • Li L, Zhang X, Lin Y, et al. Let-7b-5p inhibits breast cancer cell growth and metastasis via repression of hexokinase 2-mediated aerobic glycolysis. Cell Death Discov. 2023;9(1):114.
  • Bahojb Mahdavi SZ, Pouladi N, Amini M, et al. Let-7a-3p overexpression increases chemosensitivity to carmustine and synergistically promotes autophagy and suppresses cell survival in U87MG glioblastoma cancer cells. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(9):6903-6918.
  • Jiang J, Liu HL, Tao L, et al. Let 7d inhibits colorectal cancer cell proliferation through the CST1/p65 pathway. Int J Oncol. 2018;53(2):781-790.
  • Demirel G, Tanoglu EG, Aslıyuksek H. Evaluation of microRNA let-7b-3p expression levels in methamphetamine abuse. Rev Assoc Med Bras (1992). 2023;69(4):e20221391.
  • Dai R, Zhang L, Jin H, et al. Differential expression profile of urinary exosomal microRNAs in patients with mesangial proliferative glomerulonephritis. Aging (Albany NY). 2023;15(3):866-880.
  • Liu K, Ma L, Zhou F, et al. Identification of microRNAs related to myocardial ischemic reperfusion injury. J Cell Physiol. 2019;234(7): 11380-11390.
  • Chirshev E, Oberg KC, Ioffe YJ, Unternaehrer JJ. Let-7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer. Clin Transl Med. 2019;8(1):24.
  • Murray MJ, Bailey S, Raby KL, et al. Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma. Oncogenesis. 2014;3(2): e87.
  • Chen M, Xu R, Rai A, et al. Distinct shed microvesicle and exosome microRNA signatures reveal diagnostic markers for colorectal cancer. PLoS One. 2019;14(1):e0210003.
  • Weaver DT, Pishas KI, Williamson D, et al. Network potential identifies therapeutic miRNA cocktails in Ewing sarcoma. PLoS Comput Biol. 2021;17(10):e1008755.
  • Li Y, Dong R, Lu M, et al. Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma. Transl Lung Cancer Res. 2021;10(4):1841-1856.
  • Zhang B, Liu Y, Yu J, Lin X. Upregulation of FGF9 and NOVA1 in cancer-associated fibroblasts promotes cell proliferation, invasion and migration of triple negative breast cancer. Drug Dev Res. 2024;85(3): e22185.
  • Yotsumoto T, Maemura K, Watanabe K, et al. NRXN1 as a novel potential target of antibody-drug conjugates for small cell lung cancer. Oncotarget. 2020;11(39):3590-3600.
  • Li W, Zhou K, Li M, et al. Identification of SCN7A as the key gene associated with tumor mutation burden in gastric cancer. BMC Gastroenterol. 2022;22(1):45.
  • Ma Z, Li Z, Wang S, et al. ZMAT1 acts as a tumor suppressor in pancreatic ductal adenocarcinoma by inducing SIRT3/p53 signaling pathway. J Exp Clin Cancer Res. 2022;41(1):130.
  • Su N, Qiu H, Chen Y, Yang T, Yan Q, Wan X. miR-205 promotes tumor proliferation and invasion through targeting ESRRG in endometrial carcinoma. Oncol Rep. 2013;29(6):2297-2302.
  • Ha K, Buchan JG, Alvarado DM, et al. MYBPC1 mutations impair skeletal muscle function in zebrafish models of arthrogryposis. Hum Mol Genet. 2013;22(24):4967-4977.
  • Liu J, Song J, Li C. MYBPC1 is a key regulator for laryngeal carcinoma formation. Anticancer Drugs. 2023;34(1):1-8.
  • Zhang J, Jiang S, Gu D, et al. Identification of novel molecular subtypes and a signature to predict prognosis and therapeutic response based on cuproptosis-related genes in prostate cancer. Front Oncol. 2023;13: 1162653.
  • Pudova EA, Lukyanova EN, Nyushko KM, et al. Differentially expressed genes associated with prognosis in locally advanced lymph node-negative prostate cancer. Front Genet. 2019;10:730.
  • Hu H, Wang J, Gupta A, et al. RANKL expression in normal and malignant breast tissue responds to progesterone and is up-regulated during the luteal phase. Breast Cancer Res Treat. 2014;146(3):515-523.
Toplam 41 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Kanser Genetiği, Kanser Hücre Biyolojisi, Moleküler Hedefler
Bölüm Research Articles
Yazarlar

Murat Kaya 0000-0003-2241-7088

Esra Güzel Tanoğlu 0000-0002-0909-8935

İlknur Süer 0000-0003-1954-4190

Ömer Faruk Karataş 0000-0002-0379-2088

Şükrü Öztürk 0000-0002-8809-7462

Mehmet Yılmaz 0000-0002-6417-8292

Kıvanç Çefle 0000-0002-9420-4543

Mustafa Özen 0000-0002-6142-5294

Yayımlanma Tarihi 10 Ocak 2025
Gönderilme Tarihi 5 Kasım 2024
Kabul Tarihi 7 Aralık 2024
Yayımlandığı Sayı Yıl 2025 Cilt: 7 Sayı: 1

Kaynak Göster

AMA Kaya M, Güzel Tanoğlu E, Süer İ, Karataş ÖF, Öztürk Ş, Yılmaz M, Çefle K, Özen M. Elevated expression of let-7b-3p enhances aggressiveness of larynx squamous cell carcinoma cells. Anatolian Curr Med J / ACMJ / acmj. Ocak 2025;7(1):27-32. doi:10.38053/acmj.1579621
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