MiR-26a-5p Serves As an Oncogenic MicroRNA in Non-Small Cell Lung Cancer by Targeting FAF1

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Aug 28

PMID 32848467

Citations 16

Authors

Ming-Fan Ye

Dong Lin

Wu-Jin Li

Hai-Peng Xu

Jing Zhang

Affiliations

Soon will be listed here.

Abstract

Purpose: Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancers, with the FAS-associated factor 1 (FAF1) acting as a tumor suppressor. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we aimed to reveal the influence of miR-26a-5p on the regulation of FAF1 expression and NSCLC progression, with the motivation of identifying a potential therapeutic target for NSCLC treatment.

Methods: A dual-luciferase reporter assay was used to check for the direct targeting of FAF1 by miR-26a-3p. The miR-26a-5p inhibitor or FAF1 shRNA plasmid was transfected into A549 and H1299 cells to modulate FAF1 expression. Then, the effect of miR-26a-5p/FAF1 on cellular functions was investigated. MTT assay was used to evaluate cell viability. EdU proliferation assay and cell cycle assay were performed to analyze the effect of miR-26a-5p on cell replication and cell cycle. We used annexin V-FITC and PI to stain apoptotic cells, followed by flow cytometric analysis. Transwell and wound healing assays were performed to investigate metastasis. Moreover, the effect of miR-26a-5p/FAF1 on cancer progression was examined in vivo. Lastly, the underlying mechanism was uncovered using RT-qPCR, Western blotting, and TOP/FOP flash assay.

Results: miR-26a-5p was found to directly target FAF1 and downregulate its expression. Blocking miR-26a-5p inhibited the cell growth, migration, and invasion, but promoted cell apoptosis. In addition, this inhibited the growth of tumor in mice. FAF1 knockdown reversed the functions of miR-26a-5p. Further, miR-26a-5p/FAF1 was observed to play an important role in the Wnt signaling pathway, regulating the expression of genes such as , c-Myc, and cyclin-D1.

Conclusion: Taken together, we show that miR-26a-5p functions as an oncogenic microRNA in NSCLC by targeting FAF1 and may serve as a potential target for NSCLC treatment.

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References

Jeremic B . Standard treatment option in stage III non-small-cell lung cancer: case against trimodal therapy and consolidation drug therapy. Clin Lung Cancer. 2014; 16(2):80-5. DOI: 10.1016/j.cllc.2014.08.003. View

Jensen H, Hjerrild M, Guerra B, Larsen M, Hojrup P, Boldyreff B . Phosphorylation of the Fas associated factor FAF1 by protein kinase CK2 and identification of serines 289 and 291 as the in vitro phosphorylation sites. Int J Biochem Cell Biol. 2001; 33(6):577-89. DOI: 10.1016/s1357-2725(01)00039-5. View

Nakamura T, Hamada F, ISHIDATE T, Anai K, Kawahara K, Toyoshima K . Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level. Genes Cells. 1998; 3(6):395-403. DOI: 10.1046/j.1365-2443.1998.00198.x. View

Rotow J, Bivona T . Understanding and targeting resistance mechanisms in NSCLC. Nat Rev Cancer. 2017; 17(11):637-658. DOI: 10.1038/nrc.2017.84. View

Nohata N, Hanazawa T, Kikkawa N, Mutallip M, Fujimura L, Yoshino H . Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma. Int J Oncol. 2010; 38(1):209-17. View

Wang H, Hu Z, Chen L . Enhanced plasma miR-26a-5p promotes the progression of bladder cancer via targeting PTEN. Oncol Lett. 2018; 16(4):4223-4228. PMC: 6126335. DOI: 10.3892/ol.2018.9163. View

Vestergaard H, Christensen M, Lassen U . A systematic review of targeted agents for non-small cell lung cancer. Acta Oncol. 2017; 57(2):176-186. DOI: 10.1080/0284186X.2017.1404634. View

Ryu S, Kim E . Apoptosis induced by human Fas-associated factor 1, hFAF1, requires its ubiquitin homologous domain, but not the Fas-binding domain. Biochem Biophys Res Commun. 2001; 286(5):1027-32. DOI: 10.1006/bbrc.2001.5505. View

Lemjabbar-Alaoui H, Hassan O, Yang Y, Buchanan P . Lung cancer: Biology and treatment options. Biochim Biophys Acta. 2015; 1856(2):189-210. PMC: 4663145. DOI: 10.1016/j.bbcan.2015.08.002. View

10.

Bjorling-Poulsen M, Seitz G, Guerra B, Issinger O . The pro-apoptotic FAS-associated factor 1 is specifically reduced in human gastric carcinomas. Int J Oncol. 2003; 23(4):1015-23. View

11.

Xue J, Yang J, Luo M, Cho W, Liu X . MicroRNA-targeted therapeutics for lung cancer treatment. Expert Opin Drug Discov. 2016; 12(2):141-157. DOI: 10.1080/17460441.2017.1263298. View

12.

Kang L, Yang C, Wu H, Chen Q, Huang L, Li X . miR-26a-5p Regulates TNRC6A Expression and Facilitates Theca Cell Proliferation in Chicken Ovarian Follicles. DNA Cell Biol. 2017; 36(11):922-929. DOI: 10.1089/dna.2017.3863. View

13.

Duchartre Y, Kim Y, Kahn M . The Wnt signaling pathway in cancer. Crit Rev Oncol Hematol. 2016; 99:141-9. PMC: 5853106. DOI: 10.1016/j.critrevonc.2015.12.005. View

14.

Meza R, Meernik C, Jeon J, Cote M . Lung cancer incidence trends by gender, race and histology in the United States, 1973-2010. PLoS One. 2015; 10(3):e0121323. PMC: 4379166. DOI: 10.1371/journal.pone.0121323. View

15.

Osmani L, Askin F, Gabrielson E, Li Q . Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy. Semin Cancer Biol. 2017; 52(Pt 1):103-109. PMC: 5970946. DOI: 10.1016/j.semcancer.2017.11.019. View

16.

Li V, Ng S, Boersema P, Low T, Karthaus W, Gerlach J . Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell. 2012; 149(6):1245-56. DOI: 10.1016/j.cell.2012.05.002. View

17.

Shtutman M, Zhurinsky J, Simcha I, Albanese C, DAmico M, Pestell R . The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci U S A. 1999; 96(10):5522-7. PMC: 21892. DOI: 10.1073/pnas.96.10.5522. View

18.

Alghamdi H, Alshehri A, Farhat G . An overview of mortality & predictors of small-cell and non-small cell lung cancer among Saudi patients. J Epidemiol Glob Health. 2018; 7 Suppl 1:S1-S6. PMC: 7386448. DOI: 10.1016/j.jegh.2017.09.004. View

19.

Ryu S, Chae S, Lee K, Kim E . Identification and characterization of human Fas associated factor 1, hFAF1. Biochem Biophys Res Commun. 1999; 262(2):388-94. DOI: 10.1006/bbrc.1999.1217. View

20.

Dempke W . Targeted Therapy for NSCLC--A Double-edged Sword?. Anticancer Res. 2015; 35(5):2503-12. View