MicroRNA‑197 reverses the drug resistance of fluorouracil‑induced SGC7901 cells by targeting mitogen‑activated protein kinase 1

Xiong,Hai‑Lin; Zhou,Si‑Wei; Sun,Ai‑Hua; He,Ying; Li,Jun; Yuan,Xia

doi:10.3892/mmr.2015.4052

October-2015 Volume 12 Issue 4

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October-2015 Volume 12 Issue 4

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Article Open Access

MicroRNA‑197 reverses the drug resistance of fluorouracil‑induced SGC7901 cells by targeting mitogen‑activated protein kinase 1

Authors:
- Hai‑Lin Xiong
- Si‑Wei Zhou
- Ai‑Hua Sun
- Ying He
- Jun Li
- Xia Yuan
View Affiliations / Copyright

Affiliations: Department of Medical Oncology, Huizhou Municipal Central Hospital of Guangdong Province, Huizhou, Guangdong 516000, P.R. China

Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 5019-5025
|
Published online on: July 7, 2015

https://doi.org/10.3892/mmr.2015.4052
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Abstract

MicroRNAs (miRNAs) are a group of small non‑coding RNA molecules, which serve an important function in the development of multidrug resistance in cancer through the post‑transcriptional regulation of gene expression and RNA silencing. In the present study, the functional effects of miR‑197 were analyzed in chemo‑resistant gastric cancer cells. Low expression levels of miR‑197 were observed in the fluorouracil (5‑FU)‑resistant gastric cell line SGC7901/5‑FU when compared with those in the parental gastric cell line SGC7901. Overexpression of miR‑197 in SGC7901/5‑FU cells was identified to partially restore 5‑FU sensitivity. miRNA target prediction algorithms suggested that mitogen‑activated protein kinase 1 (MAPK1) is a candidate target gene for miR‑197. A luciferase reporter assay confirmed that miR‑197 led to silencing of the MAPK1 gene by recognizing and then specifically binding to the predicted site of the MAPK1 mRNA 3'‑untranslated region. When miR‑197 was overexpressed in SGC7901 cells, the protein levels of MAPK1 were downregulated. Furthermore, MAPK1 knockdown significantly increased the growth inhibition rate of the SGC7901/5‑FU cells compared with those in the control group. These results indicated that miR‑197 may influence the sensitivity of 5‑FU treatment in a gastric cancer cell line by targeting MAPK1.

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1	Murray CJ and Lopez AD: Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet. 349:1498–1504. 1997. View Article : Google Scholar : PubMed/NCBI
2	Cunningham D, Allum WH, Stenning SP, et al: MAGIC Trial Participants: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 355:11–20. 2006. View Article : Google Scholar : PubMed/NCBI
3	Rivera F, Vega-Villegas ME and López-Brea MF: Chemotherapy of advanced gastric cancer. Cancer Treat Rev. 33:315–324. 2007. View Article : Google Scholar : PubMed/NCBI
4	Climent J, Dimitrow P, Fridlyand J, Palacios J, Siebert R, Albertson DG, Gray JW, Pinkel D, Lluch A and Martinez-Climent JA: Deletion of chromosome 11q predicts response to anthracycline-based chemotherapy in early breast cancer. Cancer Res. 67:818–826. 2007. View Article : Google Scholar : PubMed/NCBI
5	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
6	Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH and Kim VN: MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 23:4051–4060. 2004. View Article : Google Scholar : PubMed/NCBI
7	Han J, Lee Y, Yeom KH, Kim YK, Jin H and Kim VN: The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 18:3016–3027. 2004. View Article : Google Scholar : PubMed/NCBI
8	Lee Y, Ahn C, Han J, et al: The nuclear RNase III Drosha initiates microRNA processing. Nature. 425:415–419. 2003. View Article : Google Scholar : PubMed/NCBI
9	Lee Y, Jeon K, Lee JT, Kim S and Kim VN: MicroRNA maturation: Stepwise processing and subcellular localization. EMBO J. 21:4663–4670. 2002. View Article : Google Scholar : PubMed/NCBI
10	Lund E, Güttinger S, Calado A, Dahlberg JE and Kutay U: Nuclear export of microRNA precursors. Science. 303:95–98. 2004. View Article : Google Scholar
11	Hutvágner G, McLachlan J, Pasquinelli AE, Bálint E, Tuschl T and Zamore PD: A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 293:834–838. 2001. View Article : Google Scholar : PubMed/NCBI
12	Parker JS and Barford D: Argonaute: A scaffold for the function of short regulatory RNAs. Trends Biochem Sci. 31:622–630. 2006. View Article : Google Scholar : PubMed/NCBI
13	Peters L and Meister G: Argonaute proteins: Mediators of RNA silencing. Mol Cell. 26:611–623. 2007. View Article : Google Scholar : PubMed/NCBI
14	Pillai RS, Bhattacharyya SN and Filipowicz W: Repression of protein synthesis by miRNAs: How many mechanisms? Trends Cell Biol. 17:118–126. 2007. View Article : Google Scholar : PubMed/NCBI
15	Felli N, Fontana L, Pelosi E, et al: MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA. 102:18081–18086. 2005. View Article : Google Scholar : PubMed/NCBI
16	Li J, Huang H, Sun L, et al: MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clin Cancer Res. 15:3998–4008. 2009. View Article : Google Scholar : PubMed/NCBI
17	Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R and Olson EN: The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 15:261–271. 2008. View Article : Google Scholar : PubMed/NCBI
18	Xu N, Papagiannakopoulos T, Pan G, Thomson JA and Kosik KS: MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell. 137:647–658. 2009. View Article : Google Scholar : PubMed/NCBI
19	Ma L, Young J, Prabhala H, et al: miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 12:247–256. 2010.PubMed/NCBI
20	Huh JH, Kim TH, Kim K, Song JA, Jung YJ, Jeong JY, Lee MJ, Kim YK, Lee DH and An HJ: Dysregulation of miR-106a and miR-591 confers paclitaxel resistance to ovarian cancer. Br J Cancer. 109:452–461. 2013. View Article : Google Scholar : PubMed/NCBI
21	Fang Y, Shen H, Li H, Cao Y, Qin R, Long L, Zhu X, Xie C and Xu W: miR-106a confers cisplatin resistance by regulating PTEN/Akt pathway in gastric cancer cells. Acta Biochim Biophys Sin (Shanghai). 45:963–972. 2013. View Article : Google Scholar
22	Xia L, Zhang D, Du R, et al: miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 123:372–379. 2008. View Article : Google Scholar : PubMed/NCBI
23	Fan D, Zhang X, Chen X, Mou Z, Hu J, Zhou S, Ding J and Wu K: Bird's-eye view on gastric cancer research of the past 25 years. J Gastroenterol Hepatol. 20:360–365. 2005. View Article : Google Scholar : PubMed/NCBI
24	Zhu H, Wu H, Liu X, Evans BR, Medina DJ, Liu CG and Yang JM: Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem Pharmacol. 76:582–588. 2008. View Article : Google Scholar : PubMed/NCBI
25	Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, Jiang J, Schmittgen TD and Patel T: Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology. 130:2113–2129. 2006. View Article : Google Scholar : PubMed/NCBI
26	Zhang CX, Huang S, Xu N, Fang JW, Shen P, Bao YH, Mou BH, Shi MG, Zhong XL and Xiong PJ: Phase II study of epirubicin plus oxaliplatin and infusional 5-fluorouracil as first-line combination therapy in patients with metastatic or advanced gastric cancer. Anticancer Drugs. 18:581–586. 2007. View Article : Google Scholar : PubMed/NCBI
27	Kopnin BP: Targets of oncogenes and tumor suppressors: Key for understanding basic mechanisms of carcinogenesis. Biochemistry Biokhimiia. 65:2–27. 2000.PubMed/NCBI
28	Whitmarsh AJ and Davis RJ: Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med Berl. 74:589–607. 1996. View Article : Google Scholar : PubMed/NCBI
29	Kim HG, Lee CK, Cho SM, Whang K, Cha BH, Shin JH, Song KH and Jeong SW: Neuregulin 1 up-regulates the expression of nicotinic acetylcholine receptors through the ErbB2/ErbB3-PI3K-MAPK signaling cascade in adult autonomic ganglion neurons. J Neurochem. 124:502–513. 2013. View Article : Google Scholar
30	Lewis TS, Shapiro PS and Ahn NG: Signal transduction through MAP kinase cascades. Adv Cancer Res. 74:49–139. 1998. View Article : Google Scholar : PubMed/NCBI
31	Katayama K, Yoshioka S, Tsukahara S, Mitsuhashi J and Sugimoto Y: Inhibition of the mitogen-activated protein kinase pathway results in the down-regulation of P-glycoprotein. Mol Cancer Ther. 6:2092–2102. 2007. View Article : Google Scholar : PubMed/NCBI
32	Kisucká J, Barancík M, Bohácová V and Breier A: Reversal effect of specific inhibitors of extracellular-signal regulated protein kinase pathway on P-glycoprotein mediated vincristine resistance of L1210 cells. Gen Physiol Biophys. 20:439–444. 2001.
33	Lin JC, Chang SY, Hsieh DS, Lee CF and Yu DS: Modulation of mitogen-activated protein kinase cascades by differentiation-1 protein: Acquired drug resistance of hormone independent prostate cancer cells. J Urol. 174:2022–2026. 2005. View Article : Google Scholar : PubMed/NCBI
34	Li Y, Li S, Han Y, Liu J, Zhang J, Li F, Wang Y, Liu X and Yao L: Calebin-A induces apoptosis and modulates MAPK family activity in drug resistant human gastric cancer cells. Eur J Pharmacol. 591:252–258. 2008. View Article : Google Scholar : PubMed/NCBI
35	McCubrey JA, Steelman LS, Abrams SL, Lee JT, Chang F, Bertrand FE, Navolanic PM, Terrian DM, Franklin RA, D'Assoro AB, et al: Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv Enzyme Regul. 46:249–279. 2006. View Article : Google Scholar : PubMed/NCBI
36	Hu Y, Bally M, Dragowska WH and Mayer L: Inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase enhances chemotherapeutic effects on H460 human non-small cell lung cancer cells through activation of apoptosis. Mol Cancer Ther. 2:641–649. 2003.PubMed/NCBI