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Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal miRNAs in Non-Small Cell Lung Cancer Cases

Year 2025, Volume: 9 Issue: 1, 205 - 211, 31.01.2025
https://doi.org/10.30621/jbachs.1595106

Abstract

References

  • Sabaila A, Fauconnier A, Huchon C. Chimiothérapie intrapéritonéale pressurisée en aérosol (CIPPA): Une nouvelle voie d’administration dans les carcinoses péritonéales d’origine ovarienne. Gynecol Obstet Fertil 2015;43:66–67.
  • Tuncay Goksel, Sultan Eser, Salih Z. Guclu, et al. Turkish Lung Cancer Mapping Project Study Group. Prognostic factors affecting survival in cases with lung cancer [A lung cancer mapping project in Turkey (LCMPT)]. In: European Respiratory Journal 2013. p. P2920.
  • Lee CK, Brown C, Gralla RJ, et al. Impact of EGFR Inhibitor in Non–Small Cell Lung Cancer on Progression-Free and Overall Survival: A Meta-Analysis. JNCI J Natl Cancer Inst 2013;105:595–605.
  • Onozato R, Kosaka T, Kuwano H, Sekido Y, Yatabe Y, Mitsudomi T. Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primary resected lung cancers. J Thorac Oncol 2009;4:5–11.
  • Reclusa P, Sirera R, Araujo A, et al. Exosomes genetic cargo in lung cancer: A truly Pandora’s box. Vol. 5. Translational Lung Cancer Research 2016;p. 483–491.
  • Taverna S, Giallombardo M, Gil-Bazo I, et al. Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: Critical analysis of evidence and potential role in clinical practice. Oncotarget 2016;7:28748–28760.
  • Nuzhat Z, Kinhal V, Sharma S, Rice GE, Joshi V, Salomon C. Tumour-derived exosomes as a signature of pancreatic cancer- liquid biopsies as indicators of tumor progression. Oncotarget. 2017.
  • Rolfo C, Chacartegui J, Giallombardo M, Alessandro R, Peeters M. Exosomes isolated in plasma of non-small cell lung cancer patients contain microRNA related to the EGFR pathway: Proof of concept. J Thorac Oncol 2016;11:S85.
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 2001;25:402–408.
  • Ermin S, Batum Ö, Saka Güvenç M, Diniz G, Ayrancı A, Erdoğan KM, et al. The relation between distant metastasis and genetic change type in stage IV lung adenocarcinoma patients at diagnosis. Clin Respir J 2021;15:196–202.
  • Poh M-E, Liam C-K, Rajadurai P, Chai C-S. Epithelial-to-mesenchymal transition (EMT) causes acquired resistance to afatinib in a patient with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma. J Thorac Dis 2018;10:E560–563.
  • Bach D-H, Luu T-T-T, Kim D, et al. BMP4 Upregulation Is Associated with Acquired Drug Resistance and Fatty Acid Metabolism in EGFR-Mutant Non-Small-Cell Lung Cancer Cells. Mol Ther Nucleic Acids 2018;12:817–828.
  • Lyu H, Han A, Polsdofer E, Liu S, Liu B. Understanding the biology of HER3 receptor as a therapeutic target in human cancer. Acta Pharm Sin B 2018;8:503–510.
  • Kharbanda A, Rajabi H, Jin C, Alam M, Wong K-K, Kufe D. MUC1-C confers EMT and KRAS independence in mutant KRAS lung cancer cells. Oncotarget 2014;5:8893–8905.
  • Park K-S, Raffeld M, Moon YW, et al. CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance. J Clin Invest 2014;124:3003–3015.
  • Li B, Ding C-M, Li Y-X, Peng J-C, Geng N, Qin W-W. Over-regulation of microRNA-133b inhibits cell proliferation of cisplatin-induced non-small cell lung cancer cells through PI3K/Akt and JAK2/STAT3 signaling pathways by targeting EGFR. Oncol Rep 2018;39:1227–1234.
  • Wang N, Zhang T. Downregulation of MicroRNA-135 Promotes Sensitivity of Non-Small Cell Lung Cancer to Gefitinib by Targeting TRIM16. Oncol Res 2018;26:1005–1014.
  • Iaboni M, Russo V, Fontanella R, et al. Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL. Mol Ther Nucleic Acids 2016;5:e289.
  • Pang W, Tian X, Bai F, et al. Pim-1 kinase is a target of miR-486-5p and eukaryotic translation initiation factor 4E and plays a critical role in lung cancer. Mol Cancer 2014;13:240.
  • Sun Y, Chen C, Zhang P, et al. Reduced miR-3127-5p expression promotes NSCLC proliferation/invasion and contributes to dasatinib sensitivity via the c-Abl/Ras/ERK pathway. Sci Rep 2014;4:6527.
  • Zhou Y-M, Liu J, Sun W. MiR-130a overcomes gefitinib resistance by targeting met in non-small cell lung cancer cell lines. Asian Pac J Cancer Prev 2014;15:1391–1396.
  • Gao Y, Fan X, Li W, Ping W, Deng Y, Fu X. miR-138-5p reverses gefitinib resistance in non-small cell lung cancer cells via negatively regulating G protein-coupled receptor 124. Biochem Biophys Res Commun 2014;446:179–186.
  • Li P, Ma L, Zhang Y, Ji F, Jin F. MicroRNA-137 down-regulates KIT and inhibits small cell lung cancer cell proliferation. Biomed Pharmacother 2014;68:7–12.
  • Kitamura K, Seike M, Okano T, et al. MiR-134/487b/655 cluster regulates TGF-β-induced epithelial-mesenchymal transition and drug resistance to gefitinib by targeting MAGI2 in lung adenocarcinoma cells. Mol Cancer Ther 2014;13:444–453.
  • Ping W, Gao Y, Fan X, Li W, Deng Y, Fu X. MiR-181a contributes gefitinib resistance in non-small cell lung cancer cells by targeting GAS7. Biochem Biophys Res Commun 2018;495:2482–2489.
  • Zhang H, Chen F, He Y, et al. Sensitivity of non-small cell lung cancer to erlotinib is regulated by the Notch/miR-223/FBXW7 pathway. Biosci Rep 2017;37:BSR20160478.
  • Liu Q, Yu Z, Yuan S et al. Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer. Oncotarget 2017;8:13048–13058.
  • Narita M, Shimura E, Nagasawa A, et al. Chronic treatment of non-small-cell lung cancer cells with gefitinib leads to an epigenetic loss of epithelial properties associated with reductions in microRNA-155 and -200c. Chai KX, editor. PLoS One 2017;12:e0172115.
  • Sato H, Shien K, Tomida S, et al. Targeting the miR-200c/LIN28B axis in acquired EGFR-TKI resistance non-small cell lung cancer cells harboring EMT features. Sci Rep 2017;7:40847.
  • Jin X, Chen Y, Chen H, et al. Evaluation of tumor-derived exosomal miRNA as potential diagnostic biomarkers for early-stage non-small cell lung cancer using next-generation sequencing. Clin Cancer Res 2017;23:5311–5319.
  • Rothschild SI, Gautschi O, Batliner J, Gugger M, Fey MF, Tschan MP. MicroRNA-106a targets autophagy and enhances sensitivity of lung cancer cells to Src inhibitors. Lung Cancer 2017;107:73–83.
  • Xu S, Wang T, Yang Z, et al. miR-26a desensitizes non-small cell lung cancer cells to tyrosine kinase inhibitors by targeting PTPN13. Oncotarget 2016;7:45687–45701.

Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal miRNAs in Non-Small Cell Lung Cancer Cases

Year 2025, Volume: 9 Issue: 1, 205 - 211, 31.01.2025
https://doi.org/10.30621/jbachs.1595106

Abstract

Background and Purpose: Recently, the “Epidermal Growth Factor Receptor” gene and its related pathways are potential targets in precision medicine for “Non-Small Cell Lung Cancer” cases. The presented study is a proof of concept study, which utilizes exosomal miRNAs as an easy and cheap liquid biopsy approach.
We aim to investigate, 4 exosomal miRNAs: miR-30b, miR-30c, miR-221-3p, miR-22-3p; and miR-1288 as control. They are defined in the literature previously.
Methods: Thirty-six samples from distinct Non-Small Cell Lung Cancer cases are analyzed. Exosomes are extracted from the plasma of the patients; miRNA isolation, cDNA synthesis, and real-time quantitative polymerase chain reactions are done and ∆/∆ Ct method is used for relative quantification.
Results: The control miR1288 is expressed in all of the samples except one. The two miRNA targets miR-30c and miR-22-3p produced polymerase chain reaction curves successfully. The remaining two miRNAs (miR-30b, miR-221-3p) produce weak polymerase chain reaction curves.
Conclusion: miR-30b, miR-221-3p, miR-30c, and miR-22-3p are reported to be associated with lung cancer previously, but they have not been studied in a patient series before. In our study, the exosomal miR-30c, and miR-22-3p are successfully derived from the plasma of cancer cases and they could be potential biomarkers.

References

  • Sabaila A, Fauconnier A, Huchon C. Chimiothérapie intrapéritonéale pressurisée en aérosol (CIPPA): Une nouvelle voie d’administration dans les carcinoses péritonéales d’origine ovarienne. Gynecol Obstet Fertil 2015;43:66–67.
  • Tuncay Goksel, Sultan Eser, Salih Z. Guclu, et al. Turkish Lung Cancer Mapping Project Study Group. Prognostic factors affecting survival in cases with lung cancer [A lung cancer mapping project in Turkey (LCMPT)]. In: European Respiratory Journal 2013. p. P2920.
  • Lee CK, Brown C, Gralla RJ, et al. Impact of EGFR Inhibitor in Non–Small Cell Lung Cancer on Progression-Free and Overall Survival: A Meta-Analysis. JNCI J Natl Cancer Inst 2013;105:595–605.
  • Onozato R, Kosaka T, Kuwano H, Sekido Y, Yatabe Y, Mitsudomi T. Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primary resected lung cancers. J Thorac Oncol 2009;4:5–11.
  • Reclusa P, Sirera R, Araujo A, et al. Exosomes genetic cargo in lung cancer: A truly Pandora’s box. Vol. 5. Translational Lung Cancer Research 2016;p. 483–491.
  • Taverna S, Giallombardo M, Gil-Bazo I, et al. Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: Critical analysis of evidence and potential role in clinical practice. Oncotarget 2016;7:28748–28760.
  • Nuzhat Z, Kinhal V, Sharma S, Rice GE, Joshi V, Salomon C. Tumour-derived exosomes as a signature of pancreatic cancer- liquid biopsies as indicators of tumor progression. Oncotarget. 2017.
  • Rolfo C, Chacartegui J, Giallombardo M, Alessandro R, Peeters M. Exosomes isolated in plasma of non-small cell lung cancer patients contain microRNA related to the EGFR pathway: Proof of concept. J Thorac Oncol 2016;11:S85.
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 2001;25:402–408.
  • Ermin S, Batum Ö, Saka Güvenç M, Diniz G, Ayrancı A, Erdoğan KM, et al. The relation between distant metastasis and genetic change type in stage IV lung adenocarcinoma patients at diagnosis. Clin Respir J 2021;15:196–202.
  • Poh M-E, Liam C-K, Rajadurai P, Chai C-S. Epithelial-to-mesenchymal transition (EMT) causes acquired resistance to afatinib in a patient with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma. J Thorac Dis 2018;10:E560–563.
  • Bach D-H, Luu T-T-T, Kim D, et al. BMP4 Upregulation Is Associated with Acquired Drug Resistance and Fatty Acid Metabolism in EGFR-Mutant Non-Small-Cell Lung Cancer Cells. Mol Ther Nucleic Acids 2018;12:817–828.
  • Lyu H, Han A, Polsdofer E, Liu S, Liu B. Understanding the biology of HER3 receptor as a therapeutic target in human cancer. Acta Pharm Sin B 2018;8:503–510.
  • Kharbanda A, Rajabi H, Jin C, Alam M, Wong K-K, Kufe D. MUC1-C confers EMT and KRAS independence in mutant KRAS lung cancer cells. Oncotarget 2014;5:8893–8905.
  • Park K-S, Raffeld M, Moon YW, et al. CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance. J Clin Invest 2014;124:3003–3015.
  • Li B, Ding C-M, Li Y-X, Peng J-C, Geng N, Qin W-W. Over-regulation of microRNA-133b inhibits cell proliferation of cisplatin-induced non-small cell lung cancer cells through PI3K/Akt and JAK2/STAT3 signaling pathways by targeting EGFR. Oncol Rep 2018;39:1227–1234.
  • Wang N, Zhang T. Downregulation of MicroRNA-135 Promotes Sensitivity of Non-Small Cell Lung Cancer to Gefitinib by Targeting TRIM16. Oncol Res 2018;26:1005–1014.
  • Iaboni M, Russo V, Fontanella R, et al. Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL. Mol Ther Nucleic Acids 2016;5:e289.
  • Pang W, Tian X, Bai F, et al. Pim-1 kinase is a target of miR-486-5p and eukaryotic translation initiation factor 4E and plays a critical role in lung cancer. Mol Cancer 2014;13:240.
  • Sun Y, Chen C, Zhang P, et al. Reduced miR-3127-5p expression promotes NSCLC proliferation/invasion and contributes to dasatinib sensitivity via the c-Abl/Ras/ERK pathway. Sci Rep 2014;4:6527.
  • Zhou Y-M, Liu J, Sun W. MiR-130a overcomes gefitinib resistance by targeting met in non-small cell lung cancer cell lines. Asian Pac J Cancer Prev 2014;15:1391–1396.
  • Gao Y, Fan X, Li W, Ping W, Deng Y, Fu X. miR-138-5p reverses gefitinib resistance in non-small cell lung cancer cells via negatively regulating G protein-coupled receptor 124. Biochem Biophys Res Commun 2014;446:179–186.
  • Li P, Ma L, Zhang Y, Ji F, Jin F. MicroRNA-137 down-regulates KIT and inhibits small cell lung cancer cell proliferation. Biomed Pharmacother 2014;68:7–12.
  • Kitamura K, Seike M, Okano T, et al. MiR-134/487b/655 cluster regulates TGF-β-induced epithelial-mesenchymal transition and drug resistance to gefitinib by targeting MAGI2 in lung adenocarcinoma cells. Mol Cancer Ther 2014;13:444–453.
  • Ping W, Gao Y, Fan X, Li W, Deng Y, Fu X. MiR-181a contributes gefitinib resistance in non-small cell lung cancer cells by targeting GAS7. Biochem Biophys Res Commun 2018;495:2482–2489.
  • Zhang H, Chen F, He Y, et al. Sensitivity of non-small cell lung cancer to erlotinib is regulated by the Notch/miR-223/FBXW7 pathway. Biosci Rep 2017;37:BSR20160478.
  • Liu Q, Yu Z, Yuan S et al. Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer. Oncotarget 2017;8:13048–13058.
  • Narita M, Shimura E, Nagasawa A, et al. Chronic treatment of non-small-cell lung cancer cells with gefitinib leads to an epigenetic loss of epithelial properties associated with reductions in microRNA-155 and -200c. Chai KX, editor. PLoS One 2017;12:e0172115.
  • Sato H, Shien K, Tomida S, et al. Targeting the miR-200c/LIN28B axis in acquired EGFR-TKI resistance non-small cell lung cancer cells harboring EMT features. Sci Rep 2017;7:40847.
  • Jin X, Chen Y, Chen H, et al. Evaluation of tumor-derived exosomal miRNA as potential diagnostic biomarkers for early-stage non-small cell lung cancer using next-generation sequencing. Clin Cancer Res 2017;23:5311–5319.
  • Rothschild SI, Gautschi O, Batliner J, Gugger M, Fey MF, Tschan MP. MicroRNA-106a targets autophagy and enhances sensitivity of lung cancer cells to Src inhibitors. Lung Cancer 2017;107:73–83.
  • Xu S, Wang T, Yang Z, et al. miR-26a desensitizes non-small cell lung cancer cells to tyrosine kinase inhibitors by targeting PTPN13. Oncotarget 2016;7:45687–45701.
There are 32 citations in total.

Details

Primary Language English
Subjects Gene Expression, Genetics (Other), Chest Diseases, Clinical Oncology
Journal Section Research Article
Authors

Altuğ Koç 0000-0002-8366-6806

Asım Leblebici 0000-0002-5197-6631

Haydar Soydaner Karakuş 0000-0002-3099-9172

Ceyda Aldağ This is me 0000-0003-3130-4739

Kadri Murat Erdoğan 0000-0003-0097-1424

Merve Saka Güvenç 0000-0001-8842-0381

Su Özgür 0000-0002-8993-674X

Tuncay Göksel 0000-0002-6089-1840

Yasemin Başbınar 0000-0001-9439-2217

Publication Date January 31, 2025
Submission Date December 2, 2024
Acceptance Date January 19, 2025
Published in Issue Year 2025 Volume: 9 Issue: 1

Cite

APA Koç, A., Leblebici, A., Karakuş, H. S., Aldağ, C., et al. (2025). Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal miRNAs in Non-Small Cell Lung Cancer Cases. Journal of Basic and Clinical Health Sciences, 9(1), 205-211. https://doi.org/10.30621/jbachs.1595106
AMA Koç A, Leblebici A, Karakuş HS, Aldağ C, Erdoğan KM, Saka Güvenç M, Özgür S, Göksel T, Başbınar Y. Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal miRNAs in Non-Small Cell Lung Cancer Cases. JBACHS. January 2025;9(1):205-211. doi:10.30621/jbachs.1595106
Chicago Koç, Altuğ, Asım Leblebici, Haydar Soydaner Karakuş, Ceyda Aldağ, Kadri Murat Erdoğan, Merve Saka Güvenç, Su Özgür, Tuncay Göksel, and Yasemin Başbınar. “Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal MiRNAs in Non-Small Cell Lung Cancer Cases”. Journal of Basic and Clinical Health Sciences 9, no. 1 (January 2025): 205-11. https://doi.org/10.30621/jbachs.1595106.
EndNote Koç A, Leblebici A, Karakuş HS, Aldağ C, Erdoğan KM, Saka Güvenç M, Özgür S, Göksel T, Başbınar Y (January 1, 2025) Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal miRNAs in Non-Small Cell Lung Cancer Cases. Journal of Basic and Clinical Health Sciences 9 1 205–211.
IEEE A. Koç, A. Leblebici, H. S. Karakuş, C. Aldağ, K. M. Erdoğan, M. Saka Güvenç, S. Özgür, T. Göksel, and Y. Başbınar, “Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal miRNAs in Non-Small Cell Lung Cancer Cases”, JBACHS, vol. 9, no. 1, pp. 205–211, 2025, doi: 10.30621/jbachs.1595106.
ISNAD Koç, Altuğ et al. “Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal MiRNAs in Non-Small Cell Lung Cancer Cases”. Journal of Basic and Clinical Health Sciences 9/1 (January 2025), 205-211. https://doi.org/10.30621/jbachs.1595106.
JAMA Koç A, Leblebici A, Karakuş HS, Aldağ C, Erdoğan KM, Saka Güvenç M, Özgür S, Göksel T, Başbınar Y. Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal miRNAs in Non-Small Cell Lung Cancer Cases. JBACHS. 2025;9:205–211.
MLA Koç, Altuğ et al. “Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal MiRNAs in Non-Small Cell Lung Cancer Cases”. Journal of Basic and Clinical Health Sciences, vol. 9, no. 1, 2025, pp. 205-11, doi:10.30621/jbachs.1595106.
Vancouver Koç A, Leblebici A, Karakuş HS, Aldağ C, Erdoğan KM, Saka Güvenç M, Özgür S, Göksel T, Başbınar Y. Investigation of Epidermal Growth Factor Receptor Pathway Related, Exosomal miRNAs in Non-Small Cell Lung Cancer Cases. JBACHS. 2025;9(1):205-11.