MicroRNA-26a involved in Toll-like receptor 9‑mediated lung cancer growth and migration

  • Authors:
    • De-Sheng Jiang
    • Yu-Wei Wang
    • Jing Jiang
    • Shu-Meng Li
    • Shun-Zhi Liang
    • Hong-Yan Fang
  • View Affiliations

  • Published online on: April 30, 2014     https://doi.org/10.3892/ijmm.2014.1764
  • Pages: 307-312
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Toll-like receptor 9 (TLR9) has been shown to have a significant role in cancer. MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, are involved in the development and progression of human cancers. The present study was undertaken to determine the roles of TLR9 on lung cancer and whether miR-26a is involved in TLR9‑mediated lung cancer growth and migration. The lung cancer models were elicited by injecting human lung cancer cells into the left ventricle. The expression of TLR9 and miR-26a in lung cancer tissues obtained from lung cancer patients was increased. TLR9 ligand CpG-oligodeoxynucleotides (CpG-ODN) caused an increase in the mean tumor weight and the size of tumor mass in nude mice, and the proliferation and migration of H460 human lung cancer cells. CpG-ODN also induced an increase in the expression of miR-26a in H460 cells. The overexpression of miR-26a increased the weight and size of the tumor mass in the nude mice, and the proliferation and migration of H460 cells. Expression of phosphoinositide 3 kinase (PI3K) and phosphorylation of protein kinase B (Akt) was increased after miR-26a overexpression in the H460 cells. PI3K inhibitor wortmannin (WM) or Akt inhibitor triciribine hydrate (TCN) eliminated the increase in the proliferation and migration induced by the overexpression of miR-26a in H460 cells. These results suggested that miR-26a is involved in the TLR9‑mediated growth and migration of lung cancer through the PI3K-Akt signaling pathway.

References

1 

Gosu V, Basith S, Kwon OP and Choi S: Therapeutic applications of nucleic acids and their analogues in Toll-like receptor signaling. Molecules. 17:13503–13529. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Takagi M: Toll-like receptor - a potent driving force behind rheumatoid arthritis. J Clin Exp Hematop. 51:77–92. 2011.PubMed/NCBI

3 

Chang YJ, Wu MS, Lin JT and Chen CC: Helicobacter pylori-Induced invasion and angiogenesis of gastric cells is mediated by cyclooxygenase-2 induction through TLR2/TLR9 and promoter regulation. J Immunol. 175:8242–8252. 2005. View Article : Google Scholar

4 

Eiró N1, Altadill A, Juárez LM, et al: Toll-like receptors 3, 4 and 9 in hepatocellular carcinoma: Relationship with clinicopathological characteristics and prognosis. Hepatol Res. Jun 6–2013.(Epub ahead of print).

5 

Zhang L, Qin H, Guan X, Zhang K and Liu Z: The TLR9 gene polymorphisms and the risk of cancer: evidence from a meta-analysis. PLoS One. 8:e717852013. View Article : Google Scholar : PubMed/NCBI

6 

Sorrentino R, Morello S, Giordano MG, et al: CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma. Int J Cancer. 128:2815–2822. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Droemann D, Albrecht D, Gerdes J, et al: Human lung cancer cells express functionally active Toll-like receptor 9. Respir Res. 6:12005. View Article : Google Scholar : PubMed/NCBI

8 

Belmont L, Rabbe N, Antoine M, et al: Expression of TLR9 in tumor-infiltrating mononuclear cells enhances angiogenesis and is associated with a worse survival in lung cancer. Int J Cancer. 134:765–777. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Ren T, Wen ZK, Liu ZM, Liang YJ, Guo ZL and Xu L: Functional expression of TLR9 is associated to the metastatic potential of human lung cancer cell: functional active role of TLR9 on tumor metastasis. Cancer Biol Ther. 6:1704–1709. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Lee RC, Feinbaum RL and Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993.

12 

Cuellar TL and McManus MT: MicroRNAs and endocrine biology. J Endocrinol. 187:327–332. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Krol J, Loedige I and Filipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 11:597–610. 2010.PubMed/NCBI

14 

Miller AM, Gilchrist DS, Nijjar J, et al: MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice. PLoS One. 8:e723242013. View Article : Google Scholar : PubMed/NCBI

15 

Ma Y, Bao-Han W, Lv X, et al: MicroRNA-34a mediates the autocrine signaling of PAR2-activating proteinase and its role in colonic cancer cell proliferation. PLoS One. 8:e723832013. View Article : Google Scholar : PubMed/NCBI

16 

Yang X, Du WW, Li H, et al: Both mature miR-17-5p and passenger strand miR-17-3p target TIMP3 and induce prostate tumor growth and invasion. Nucleic Acids Res. 41:9688–9704. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Qian X, Zhao P, Li W, et al: MicroRNA-26a promotes tumor growth and angiogenesis in glioma by directly targeting prohibitin. CNS Neurosci Ther. 19:804–812. 2013.PubMed/NCBI

18 

Zhang J, Han C and Wu T: MicroRNA-26a promotes cholangiocarcinoma growth by activating β-catenin. Gastroenterology. 143:246–256. e2482012.PubMed/NCBI

19 

Savry A, Carre M, Berges R, et al: Bcl-2-enhanced efficacy of microtubule-targeting chemotherapy through Bim overexpression: implications for cancer treatment. Neoplasia. 15:49–60. 2013.

20 

Bhattacharya D and Yusuf N: Expression of Toll-like receptors on breast tumors: taking a toll on tumor microenvironment. Int J Breast Cancer. 2012:7165642012. View Article : Google Scholar : PubMed/NCBI

21 

He W, Liu Q, Wang L, Chen W, Li N and Cao X: TLR4 signaling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance. Mol Immunol. 44:2850–2859. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Min R, Zun Z, Siyi L, et al: Increased expression of Toll-like receptor-9 has close relation with tumour cell proliferation in oral squamous cell carcinoma. Arch Oral Biol. 56:877–884. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar

24 

Majumder S and Jacob ST: Emerging role of microRNAs in drug-resistant breast cancer. Gene Expr. 15:141–151. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Minguez B and Lachenmayer A: Diagnostic and prognostic molecular markers in hepatocellular carcinoma. Dis Markers. 31:181–190. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Chen R, Alvero AB, Silasi DA, et al: Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells. Oncogene. 27:4712–4723. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Wendlandt EB, Graff JW, Gioannini TL, McCaffrey AP and Wilson ME: The role of microRNAs miR-200b and miR-200c in TLR4 signaling and NF-κB activation. Innate Immun. 18:846–855. 2012.PubMed/NCBI

28 

Chen R, Alvero AB, Silasi DA, Steffensen KD and Mor G: Cancers take their Toll - the function and regulation of Toll-like receptors in cancer cells. Oncogene. 27:225–233. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Xu L, Zhou Y, Liu Q, et al: CXCR4/SDF-1 pathway is crucial for TLR9 agonist enhanced metastasis of human lung cancer cell. Biochem Biophys Res Commun. 382:571–576. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Tserel L, Runnel T, Kisand K, et al: MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of Toll-like receptor 4. J Biol Chem. 286:26487–26495. 2011. View Article : Google Scholar

31 

Chen X and Zhou JY, Zhao J, Chen JJ, Ma SN and Zhou JY: Crizotinib overcomes hepatocyte growth factor-mediated resistance to gefitinib in EGFR-mutant non-small-cell lung cancer cells. Anticancer Drugs. 24:1039–1046. 2013. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

July 2014
Volume 34 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Jiang, D., Wang, Y., Jiang, J., Li, S., Liang, S., & Fang, H. (2014). MicroRNA-26a involved in Toll-like receptor 9‑mediated lung cancer growth and migration. International Journal of Molecular Medicine, 34, 307-312. https://doi.org/10.3892/ijmm.2014.1764
MLA
Jiang, D., Wang, Y., Jiang, J., Li, S., Liang, S., Fang, H."MicroRNA-26a involved in Toll-like receptor 9‑mediated lung cancer growth and migration". International Journal of Molecular Medicine 34.1 (2014): 307-312.
Chicago
Jiang, D., Wang, Y., Jiang, J., Li, S., Liang, S., Fang, H."MicroRNA-26a involved in Toll-like receptor 9‑mediated lung cancer growth and migration". International Journal of Molecular Medicine 34, no. 1 (2014): 307-312. https://doi.org/10.3892/ijmm.2014.1764