Volume 26, Issue 3 (5-2022)                   IBJ 2022, 26(3): 209-218 | Back to browse issues page

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Zafari V, Asadi M, Bakhtiyari N, Sadeghzadeh M, Khalili M, Zarredar H, et al . Regulatory Effect of let-7f Transfection in Non-Small Cell Lung Cancer on its Candidate Target Genes. IBJ. 2022; 26 (3) :209-218
URL: http://ibj.pasteur.ac.ir/article-1-3534-en.html
Background: Let-7f has essential impacts on biological processes; however, its biological and molecular functions in lung cancer pathogenesis have yet been remained unclear. We aimed to investigate the expression level of let-7f and its candidate target genes both in lung cancer tissues and A549 cell line.
Methods: Bioinformatics databases were first used to select candidate target genes of let-7f. Then the relative gene and protein expressions of let-7f and its target genes, including HMGA2, ARID3B, SMARCAD1, and FZD3, were measured in lung tissues of Non-Small Cell Lung Cancer (NSCLC) patients and A549 cell line using quantitative real-time PCR and Western blotting. The electroporation method was used to transfect A549 cells with let-7f mimic and microRNA inhibitor. The impact of let-7f transfection on the viability of A549 cells was assessed using MTT assay. The expression data of studied genes were analyzed statistically
Results: Results indicated significant downregulated expression level of let-7f-5p (p = 0.0013) and upregulated level of the HMGA2 and FZD3 in NSCLC cases (p < 0.05). In A549 cells, after transfection with let-7f mimic, the expression of both mRNA and protein levels of HMGA2, ARID3B, SMARCAD1, and FZD3 decreased. Also, the overexpression of let-7f significantly inhibited the A549 cell proliferation and viability (p = 0.017).
Conclusion: Our findings exhibited the high value of let-7f and HMGA2 as biomarkers for NSCLC. The let-7f, as a major tumor suppressor regulatory factor via direct targeting genes (e.g. HMGA2), inhibits lung cancer cell viability and proliferation and could serve as a marker for the early diagnostic of NSCLC.
Type of Study: Full Length | Subject: Cancer Biology

1. Bade BC, Cruz CSD. Lung cancer 2020: epidemiology, etiology, and prevention. Clinics in chest medicine 2020; 41(1): 1-24. [DOI:10.1016/j.ccm.2019.10.001]
2. Gridelli C, Rossi A, Carbone DP, Guarize J, Karachaliou N, Mok T, Petrella F, Spaggiari L, Rosell R. Non-small-cell lung cancer. Nature reviews disease primers 2015; 1(1): 1-16. [DOI:10.1038/nrdp.2015.9]
3. Zarredar H, Pashapour S, Ansarin K, Khalili M, Baghban R, Farajnia S. Combination therapy with KRAS siRNA and EGFR inhibitor AZD8931 suppresses lung cancer cell growth in vitro. Journal of cellular physiology 2019; 234(2): 1560-15666. [DOI:10.1002/jcp.27021]
4. Du Q, Li E, Liu Y, Xie W, Huang C, Song J, Zhang W, Zheng Y, Wang H, Wang Q. CTAPIII/CXCL 7: a novel biomarker for early diagnosis of lung cancer. Cancer medicine 2018; 7(2): 325-335. [DOI:10.1002/cam4.1292]
5. Neagu M, Constantin C, Cretoiu SM, Zurac S. miRNAs in the Diagnosis and Prognosis of Skin Cancer. Frontiers in cell and developmental biology 2020; 8: 71. [DOI:10.3389/fcell.2020.00071]
6. Wojczakowski W, Kobylarek D, Lindner J, Limphaibool N, Kaczmarek M. MicroRNAs-novel biomarkers for malignant pleural effusions. Contemporary oncology 2019; 23(3): 133. [DOI:10.5114/wo.2019.89241]
7. Yang X, Zhang Z, Zhang L, Zhou L. MicroRNA hsa-mir-3923 serves as a diagnostic and prognostic biomarker for gastric carcinoma. Scientific reports 2020; 10(1): 1-17. [DOI:10.1038/s41598-020-61633-8]
8. Regouc M, Belge G, Lorch A, Dieckmann KP, Pichler M. Non-coding microRNAs as novel potential tumor markers in testicular cancer. Cancers 2020; 12(3): 749. [DOI:10.3390/cancers12030749]
9. O'Shea JJ, Paul WE. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 2010; 327(5969): 1098-1102. [DOI:10.1126/science.1178334]
10. Liang S, He L, Zhao X, Miao Y, Gu Y, Guo C, Xue Z, Dou W, Hu F, Wu K, Nie Y, Fan D. MicroRNA let-7f inhibits tumor invasion and metastasis by targeting MYH9 in human gastric cancer. PloS one 2011; 6(4): e18409. [DOI:10.1371/journal.pone.0018409]
11. Perdas E, Stawski R, Kaczka K, Zubrzycka M. Analysis of let-7 family miRNA in plasma as potential predictive biomarkers of diagnosis for papillary thyroid cancer. Diagnostics 2020; 10(3): 130. [DOI:10.3390/diagnostics10030130]
12. Yan S, Han X, Xue H, Zhang P, Guo X, Li T, Guo X, Yuan G, Deng L, Li G. Let-7f inhibits glioma cell proliferation, migration, and invasion by targeting periostin. Journal of cellular biochemistry 2015; 116(8): 1680-1692. [DOI:10.1002/jcb.25128]
13. Zheng H, Zhang L, Zhao Y, Yang D, Song F, Wen Y, Hao Q, Hu Z, Zhang W, Chen K. Plasma miRNAs as diagnostic and prognostic biomarkers for ovarian cancer. PloS one 2013; 8(11): e77853. [DOI:10.1371/journal.pone.0077853]
14. Ge YF, Sun J, Jin CJ, Cao BQ, Jiang ZF, Shao JF. AntagomiR-27a targets FOXO3a in glioblastoma and suppresses U87 cell growth in vitro and in vivo. Asian pacific journal of cancer prevention 2013; 14(2): 963-968. [DOI:10.7314/APJCP.2013.14.2.963]
15. Sadri Nahand J, Bokharaei-Salim F, Salmaninejad A, Nesaei A, Mohajeri F, Moshtzan A, Tabibzadeh A, Karimzadeh M, Moghoofei M, Marjani A, Yaghoubi S, Keyvani H. microRNAs: Key players in virus-associated hepatocellular carcinoma. Journal of cellular physiology 2019; 234(8): 12188-12225. [DOI:10.1002/jcp.27956]
16. Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX, Shao JY. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 2008; 14(11): 2348-2360. [DOI:10.1261/rna.1034808]
17. Zhang S, Mo Q, Wang X. Oncological role of HMGA2. International journal of oncology 2019; 55(4): 775-788. [DOI:10.3892/ijo.2019.4856]
18. Shee K, Seigne JD, Karagas MR, Marsit CJ, Hinds JW, Schned AR, Pettus JR, Armstrong DA, Miller TW, Andrew AS. Identification of Let-7f-5p as a novel biomarker of recurrence in non-muscle invasive bladder cancer. Cancer biomarkers 2020; 29(1): 101-110. [DOI:10.3233/CBM-191322]
19. White NM, Bui A, Mejia-Guerrero S, Chao J, Soosaipillai A, Youssef Y, Mankaruos M, Honey RJ, Stewart R, Pace KT, Sugar L , Diamandis EP, Doré J, Yousef GM. Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs. Biological chemistry 2010; 391(4): 411-423. [DOI:10.1515/bc.2010.041]
20. Yousef GM, Diamandis EP. Expanded human tissue kallikrein family-a novel panel of cancer biomarkers. Tumor biology 2002; 23(3): 185-192. [DOI:10.1159/000064027]
21. Di Fazio P, Maass M, Roth S, Meyer C, Grups J, Rexin P, et al. Expression of hsa-let-7b-5p, hsa-let-7f-5p, and hsa-miR-222-3p and their putative targets HMGA2 and CDKN1B in typical and atypical carcinoid tumors of the lung. Tumour biology 2017; 39(10):1010428317728417. [DOI:10.1177/1010428317728417]
22. Zhao N, Liu Y, Chang Z, Li K, Zhang R, Zhou Y, Qiu F, Han X, Xu Y. Identification of biomarker and co-regulatory motifs in lung adenocarcinoma based on differential interactions. PLoS one 2015; 10(9): e0139165. [DOI:10.1371/journal.pone.0139165]
23. Cinkornpumin J, Roos M, Nguyen L, Liu X, Gaeta X, Lin S, Chan DN, Liu A, Gregory RI, Jung M, Chute J, Zhu H, Lowry WE. A small molecule screen to identify regulators of let-7 targets. Scietific reports; 2017; 7: Article number: 15973. [DOI:10.1038/s41598-017-16258-9]

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