MiR-449a Regulates the Cell Migration and Invasion of Human Non-small Cell Lung Carcinoma by Targeting ADAM10

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Jun 14

PMID 31190882

Citations 14

Authors

Haining Meng

Qiao Huang

Xijin Zhang

Jiawei Huang

Ruowu Shen

Bei Zhang

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) are non-coding small RNAs that have been shown to play a key role in the development of many tumors. However, its specific mechanism of action in non-small cell lung cancer (NSCLC) is not very clear. This study was to identify the effect of miRNA-449a on NSCLC invasion and migration. We used quantitative real-time PCR experiments to demonstrate that miRNA-449a is down-regulated in NSCLC tissues and cell lines. We also used the Transwell assay to detect cell invasion and migration, and the Western Blot assay was used to detect protein expression. The dual luciferase assay was used to detect the targeting relationship between miR-449a and A Disintegrin And Metalloproteinases 10 (ADAM10). Our experiments demonstrated that miRNA-449a was down-regulated in NSCLC tissues and cell lines. When miRNA-449a was up-regulated in NSCLC cells, the invasion and migration ability of the cells was weakened, and the expression of ADAM10 was decreased. After down-regulation of miRNA-449a, the cell's invasion and migration ability was enhanced, and the expression of ADAM10 was increased. Through dual luciferase assays, we also found that miRNA-449a can target ADAM10 to delay the progression of epithelial-mesenchymal transition (EMT) and inhibit invasion and migration. Our experiments demonstrated that miRNA-449a acted as a tumor suppressor gene through inhibiting the expression of ADAM10 in NSCLC.

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References

Seals D, Courtneidge S . The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev. 2003; 17(1):7-30. DOI: 10.1101/gad.1039703. View

McCulloch D, Akl P, Samaratunga H, Herington A, Odorico D . Expression of the disintegrin metalloprotease, ADAM-10, in prostate cancer and its regulation by dihydrotestosterone, insulin-like growth factor I, and epidermal growth factor in the prostate cancer cell model LNCaP. Clin Cancer Res. 2004; 10(1 Pt 1):314-23. DOI: 10.1158/1078-0432.ccr-0846-3. View

Spira A, Ettinger D . Multidisciplinary management of lung cancer. N Engl J Med. 2004; 350(4):379-92. DOI: 10.1056/NEJMra035536. View

Bartel D . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. View

De Leyn P, Decker G . [Surgical treatment of non-small cell lung cancer]. Rev Mal Respir. 2004; 21(5 Pt 1):971-82. DOI: 10.1016/s0761-8425(04)71479-5. View

Reiss K, Maretzky T, Ludwig A, Tousseyn T, De Strooper B, Hartmann D . ADAM10 cleavage of N-cadherin and regulation of cell-cell adhesion and beta-catenin nuclear signalling. EMBO J. 2005; 24(4):742-52. PMC: 549617. DOI: 10.1038/sj.emboj.7600548. View

Huovila A, Turner A, Pelto-Huikko M, Karkkainen I, Ortiz R . Shedding light on ADAM metalloproteinases. Trends Biochem Sci. 2005; 30(7):413-22. DOI: 10.1016/j.tibs.2005.05.006. View

Ko S, Lin S, Wong Y, Liu C, Chang K, Liu T . Increase of disintergin metalloprotease 10 (ADAM10) expression in oral squamous cell carcinoma. Cancer Lett. 2005; 245(1-2):33-43. DOI: 10.1016/j.canlet.2005.10.019. View

Tousseyn T, Jorissen E, Reiss K, Hartmann D . (Make) stick and cut loose--disintegrin metalloproteases in development and disease. Birth Defects Res C Embryo Today. 2006; 78(1):24-46. DOI: 10.1002/bdrc.20066. View

10.

Reiss K, Ludwig A, Saftig P . Breaking up the tie: disintegrin-like metalloproteinases as regulators of cell migration in inflammation and invasion. Pharmacol Ther. 2006; 111(3):985-1006. DOI: 10.1016/j.pharmthera.2006.02.009. View

11.

Gavert N, Sheffer M, Raveh S, Spaderna S, Shtutman M, Brabletz T . Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis. Cancer Res. 2007; 67(16):7703-12. DOI: 10.1158/0008-5472.CAN-07-0991. View

12.

Ou S, Zell J, Ziogas A, Anton-Culver H . Prognostic factors for survival of stage I nonsmall cell lung cancer patients : a population-based analysis of 19,702 stage I patients in the California Cancer Registry from 1989 to 2003. Cancer. 2007; 110(7):1532-41. DOI: 10.1002/cncr.22938. View

13.

Schirrmeister W, Gnad T, Wex T, Higashiyama S, Wolke C, Naumann M . Ectodomain shedding of E-cadherin and c-Met is induced by Helicobacter pylori infection. Exp Cell Res. 2009; 315(20):3500-8. DOI: 10.1016/j.yexcr.2009.07.029. View

14.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

15.

Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M . miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 2011; 9(7):824-33. DOI: 10.1158/1541-7786.MCR-10-0529. View

16.

Doberstein K, Pfeilschifter J, Gutwein P . The transcription factor PAX2 regulates ADAM10 expression in renal cell carcinoma. Carcinogenesis. 2011; 32(11):1713-23. DOI: 10.1093/carcin/bgr195. View

17.

Guo J, He L, Yuan P, Wang P, Lu Y, Tong F . ADAM10 overexpression in human non-small cell lung cancer correlates with cell migration and invasion through the activation of the Notch1 signaling pathway. Oncol Rep. 2012; 28(5):1709-18. DOI: 10.3892/or.2012.2003. View

18.

Weber S, Saftig P . Ectodomain shedding and ADAMs in development. Development. 2012; 139(20):3693-709. DOI: 10.1242/dev.076398. View

19.

Luo W, Huang B, Li Z, Li H, Sun L, Zhang Q . MicroRNA-449a is downregulated in non-small cell lung cancer and inhibits migration and invasion by targeting c-Met. PLoS One. 2013; 8(5):e64759. PMC: 3667122. DOI: 10.1371/journal.pone.0064759. View

20.

Chen J, Zhou J, Chen X, Yang B, Wang D, Yang P . miRNA-449a is downregulated in osteosarcoma and promotes cell apoptosis by targeting BCL2. Tumour Biol. 2015; 36(10):8221-9. DOI: 10.1007/s13277-015-3568-y. View