MicroRNA‑25 contributes to cisplatin resistance in gastric cancer cells by inhibiting forkhead box O3a

He,Jingbo; Qi,Huixiong; Chen,Fang; Cao,Chuanhua

doi:10.3892/ol.2017.6982

MicroRNA‑25 contributes to cisplatin resistance in gastric cancer cells by inhibiting forkhead box O3a

Authors:
- Jingbo He
- Huixiong Qi
- Fang Chen
- Chuanhua Cao
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Affiliations: Department of Oncology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, Hubei 441021, P.R. China, Department of Gerontology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
Published online on: September 18, 2017 https://doi.org/10.3892/ol.2017.6982
Pages: 6097-6102

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Abstract

Gastric cancer (GC) is a common type of malignancy worldwide, and chemotherapeutic resistance accounts for the majority of the failures in clinical treatment. MicroRNAs (miRs) are a class of small non‑coding RNAs, which serve essential roles in GC. The present study aimed to investigate the potential role of miR‑25 in the cisplatin sensitivity of GC cells. The expression level of miR‑25 was significantly upregulated in the cisplatin‑resistant GC cell line SGC‑7901/DDP compared with the SGC‑7901 parental cell line. Overexpression of miR‑25 significantly enhanced cell cycle progression and decreased the sensitivity of SGC‑7901 cells to cisplatin, whereas inhibition of miR‑25 in the SGC‑7901/DDP cisplatin‑resistant cells resulted in cell cycle arrest at the G0/G1 phase and significantly increased drug sensitivity. Furthermore, the tumor suppressor forkhead box O3a (FOXO3a) was identified as a direct target gene of miR‑25 by luciferase assay and western blot analysis, and was shown to mediate the drug‑resistance phenotype of GC cells. These findings suggest that upregulation of miR‑25 is important for GC cells to establish a cisplatin‑resistant phenotype via a FOXO3a‑dependent mechanism. Therefore, targeting miR‑25 may be a promising therapeutic approach to treat patients with cisplatin‑resistant GC.

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1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Silberman H: Perioperative adjunctive treatment in the management of operable gastric cancer. J Surg Oncol. 90(174–186): 186–187. 2005.
3	Arnason T and Harkness T: Development, Maintenance and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters and HIF1. Cancers (Basel). 7:2063–2082. 2015. View Article : Google Scholar : PubMed/NCBI
4	Dasari S and Tchounwou PB: Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol. 740:364–378. 2014. View Article : Google Scholar : PubMed/NCBI
5	Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, Harel-Bellan A, Castedo M and Kroemer G: Systems biology of cisplatin resistance: Past, present and future. Cell Death Dis. 5:e12572014. View Article : Google Scholar : PubMed/NCBI
6	Dehghanzadeh R, Jadidi-Niaragh F, Gharibi T and Yousefi M: MicroRNA-induced drug resistance in gastric cancer. Biomed Pharmacother. 74:191–199. 2015. View Article : Google Scholar : PubMed/NCBI
7	Gong J, Cui Z, Li L, Ma Q, Wang Q, Gao Y and Sun H: MicroRNA-25 promotes gastric cancer proliferation, invasion and migration by directly targeting F-box and WD-40 Domain Protein 7, FBXW7. Tumour Biol. 36:7831–7840. 2015. View Article : Google Scholar : PubMed/NCBI
8	Zhang M, Wang X, Li W and Cui Y: miR-107 and miR-25 simultaneously target LATS2 and regulate proliferation and invasion of gastric adenocarcinoma (GAC) cells. Biochem Biophys Res Commun. 460:806–812. 2015. View Article : Google Scholar : PubMed/NCBI
9	Zhao H, Wang Y, Yang L, Jiang R and Li W: MiR-25 promotes gastric cancer cells growth and motility by targeting RECK. Mol Cell Biochem. 385:207–213. 2014. View Article : Google Scholar : PubMed/NCBI
10	Li BS, Zuo QF, Zhao YL, Xiao B, Zhuang Y, Mao XH, Wu C, Yang SM, Zeng H, Zou QM and Guo G: MicroRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1 and correlates with poor survival. Oncogene. 34:2556–2565. 2015. View Article : Google Scholar : PubMed/NCBI
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
12	Xu X, Zhang Y, Liu Z, Zhang X and Jia J: miRNA-532-5p functions as an oncogenic microRNA in human gastric cancer by directly targeting RUNX3. J Cell Mol Med. 20:95–103. 2016. View Article : Google Scholar : PubMed/NCBI
13	Liu W, An J, Li K and Hou H: MiR-429 regulates gastric cancer cell invasiveness through ZEB proteins. Tumour Biol. 2015.(Epub ahead of print).
14	Nho RS and Hergert P: FoxO3a and disease progression. World J Biol Chem. 5:346–354. 2014. View Article : Google Scholar : PubMed/NCBI
15	Huang H and Tindall DJ: FOXO factors: A matter of life and death. Future Oncol. 2:83–89. 2006. View Article : Google Scholar : PubMed/NCBI
16	Dijkers PF, Medema RH, Pals C, Banerji L, Thomas NS, Lam EW, Burgering BM, Raaijmakers JA, Lammers JW, Koenderman L and Coffer PJ: Forkhead transcription factor FKHR-L1 modulates cytokine-dependent transcriptional regulation of p27 (KIP1). Mol Cell Biol. 20:9138–9148. 2000. View Article : Google Scholar : PubMed/NCBI
17	Rathbone CR, Booth FW and Lees SJ: FoxO3a preferentially induces p27^Kip1 expression while impairing muscle precursor cell-cycle progression. Muscle Nerve. 37:84–89. 2008. View Article : Google Scholar : PubMed/NCBI
18	Ray A, James MK, Larochelle S, Fisher RP and Blain SW: p27^Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent modes. Mol Cell Biol. 29:986–999. 2009. View Article : Google Scholar : PubMed/NCBI
19	Borriello A, Cucciolla V, Oliva A, Zappia V and Ragione F Della: p27^Kip1 metabolism: A fascinating labyrinth. Cell cycle. 6:1053–1061. 2007. View Article : Google Scholar : PubMed/NCBI
20	Park SH, Jang KY, Kim MJ, Yoon S, Jo Y, Kwon SM, Kim KM, Kwon KS, Kim CY and Woo HG: Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications. Oncotarget. 6:44819–44831. 2015. View Article : Google Scholar : PubMed/NCBI
21	Yu S, Yu Y, Sun Y, Wang X, Luo R, Zhao N, Zhang W, Li Q, Cui Y, Wang Y, et al: Activation of FOXO3a suggests good prognosis of patients with radically resected gastric cancer. Int J Clin Exp Pathol. 8:2963–2970. 2015.PubMed/NCBI