MicroRNA-205 suppresses the invasion and epithelial-mesenchymal transition of human gastric cancer cells

Xu,Chang; Li,Ming'e; Zhang,Lin; Bi,Yueyang; Wang,Peiyuan; Li,Jun; Jiang,Xingyue

doi:10.3892/mmr.2016.5118

MicroRNA-205 suppresses the invasion and epithelial-mesenchymal transition of human gastric cancer cells

Authors:
- Chang Xu
- Ming'e Li
- Lin Zhang
- Yueyang Bi
- Peiyuan Wang
- Jun Li
- Xingyue Jiang
View Affiliations

Affiliations: Department of Radiology, Binzhou Medical University, Binzhou, Shandong 256603, P.R. China, Department of Gerontology, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China, Department of Radiology, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China, Department of Respiratory Medicine, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China
Published online on: April 13, 2016 https://doi.org/10.3892/mmr.2016.5118
Pages: 4767-4773

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Distant metastasis is the predominant pattern of gastric cancer (GC) recurrence, and is the most common cause of cancer‑associated mortality. Accumulating evidence has suggested that aberrant activation of epithelial‑mesenchymal transition has a crucial role in the genesis, invasion and metastasis of various types of cancer, including GC. Using Cell Counting kit‑8 and Transwell assays, the effects of microRNA (miR)‑205 on the proliferation, migration and invasion of NCI‑H87 GC cells were determined, and the potential underlying mechanisms were explored. The results of the present study demonstrated that miR‑205, which has been reported to function as a tumor suppressor in various types of cancer, significantly suppressed the migration and invasion of GC cells, which may be correlated with its suppressive effects on EMT. Upon transfection with miR‑205, the epithelial marker CDH1 (E‑cadherin) was upregulated, and the mesenchymal markers CDH2 (N‑cadherin) and vimentin were suppressed. Furthermore, zinc‑finger E‑box‑binding homeobox factor‑1 (ZEB1) was identified as a putative target gene of miR‑205 in GC, which may be associated with its suppressive effects. The results of the present study may provide novel diagnostic and therapeutic options for the treatment of human GC.

View Figures

View References

1	Gill RS, Al-Adra DP, Nagendran J, Campbell S, Shi X, Haase E and Schiller D: Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive surgery and HIPEC: A systematic review of survival, mortality, and morbidity. J Surg Oncol. 104:692–698. 2011. View Article : Google Scholar : PubMed/NCBI
2	Kanat O and O'Neil BH: Metastatic gastric cancer treatment: A little slow but worthy progress. Med Oncol. 30:4642013. View Article : Google Scholar : PubMed/NCBI
3	Christiansen JJ and Rajasekaran AK: Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 66:8319–8326. 2006. View Article : Google Scholar : PubMed/NCBI
4	Klymkowsky MW and Savagner P: Epithelial-mesenchymal transition: A cancer researcher's conceptual friend and foe. Am J Pathol. 174:1588–1593. 2009. View Article : Google Scholar : PubMed/NCBI
5	Montemayor-Garcia C, Hardin H, Guo Z, Larrain C, Buehler D, Asioli S, Chen H and Lloyd RV: The role of epithelial mesenchymal transition markers in thyroid carcinoma progression. Endocr Pathol. 24:206–212. 2013. View Article : Google Scholar : PubMed/NCBI
6	Liang Q, Li L, Zhang J, Lei Y, Wang L, Liu DX, Feng J, Hou P, Yao R, Zhang Y, et al: CDK5 is essential for TGF-β1-induced epithelial-mesenchymal transition and breast cancer progression. Sci Rep. 3:29322013. View Article : Google Scholar
7	Zhao L, Li W, Zang W, Liu Z, Xu X, Yu H, Yang Q and Jia J: JMJD2B promotes epithelial-mesenchymal transition by cooperating with β-catenin and enhances gastric cancer metastasis. Clin Cancer Res. 19:6419–6429. 2013. View Article : Google Scholar : PubMed/NCBI
8	Ryu HS, Park do J, Kim HH, Kim WH and Lee HS: Combination of epithelial-mesenchymal transition and cancer stem cell-like phenotypes has independent prognostic value in gastric cancer. Hum Pathol. 43:520–528. 2012. View Article : Google Scholar
9	Hazan RB, Qiao R, Keren R, Badano I and Suyama K: Cadherin switch in tumor progression. Ann NY Acad Sci. 1014:155–163. 2004. View Article : Google Scholar : PubMed/NCBI
10	Garg M: Targeting microRNAs in epithelial-to-mesenchymal transition-induced cancer stem cells: Therapeutic approaches in cancer. Expert Opin Ther Targets. 19:285–297. 2015. View Article : Google Scholar : PubMed/NCBI
11	Kalogirou C, Spahn M, Krebs M, Joniau S, Lerut E, Burger M, Scholz CJ, Kneitz S, Riedmiller H and Kneitz B: MiR-205 is progressively down-regulated in lymph node metastasis but fails as a prognostic biomarker in high-risk prostate cancer. Int J Mol Sci. 14:21414–21434. 2013. View Article : Google Scholar : PubMed/NCBI
12	Tucci P, Agostini M, Grespi F, Markert EK, Terrinoni A, Vousden KH, Muller PA, Dötsch V, Kehrloesser S, Sayan BS, et al: Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer. Proc Natl Acad Sci USA. 109:15312–15317. 2012. View Article : Google Scholar : PubMed/NCBI
13	Yi R, O'Carroll D, Pasolli HA, Zhang Z, Dietrich FS, Tarakhovsky A and Fuchs E: Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat Genet. 38:356–362. 2006. View Article : Google Scholar : PubMed/NCBI
14	Ason B, Darnell DK, Wittbrodt B, Berezikov E, Kloosterman WP, Wittbrodt J, Antin PB and Plasterk RH: Differences in vertebrate microRNA expression. Proc Natl Acad Sci USA. 103:14385–14389. 2006. View Article : Google Scholar : PubMed/NCBI
15	Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y and Goodall GJ: The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 10:593–601. 2008. View Article : Google Scholar : PubMed/NCBI
16	Fassina A, Cappellesso R, Guzzardo V, Dalla Via L, Piccolo S, Ventura L and Fassan M: Epithelial-mesenchymal transition in malignant mesothelioma. Mod Pathol. 25:86–99. 2012. View Article : Google Scholar
17	Yin WZ, Li F, Zhang L, Ren XP, Zhang N and Wen JF: Down-regulation of microRNA-205 promotes gastric cancer cell proliferation. Eur Rev Med Pharmacol Sci. 18:1027–1032. 2014.PubMed/NCBI
18	Schmittgen TD, Zakrajsek BA, Mills AG, Gorn V, Singer MJ and Reed MW: Quantitative reverse transcription-polymerase chain reaction to study mRNA decay: Comparison of endpoint and real-time methods. Anal Biochem. 285:194–204. 2000. View Article : Google Scholar : PubMed/NCBI
19	Lee JY, Park MK, Park JH, Lee HJ, Shin DH, Kang Y, Lee CH and Kong G: Loss of the polycomb protein Mel-18 enhances the epithelial-mesenchymal transition by ZEB1 and ZEB2 expression through the downregulation of miR-205 in breast cancer. Oncogene. 33:1325–1335. 2014. View Article : Google Scholar
20	Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, Waldvogel B, Vannier C, Darling D, zur Hausen A, et al: The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol. 11:1487–1495. 2009. View Article : Google Scholar : PubMed/NCBI
21	Thiery JP and Sleeman JP: Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 7:131–142. 2006. View Article : Google Scholar : PubMed/NCBI
22	Kong YW, Ferland-McCollough D, Jackson TJ and Bushell M: microRNAs in cancer management. Lancet Oncol. 13:e249–e258. 2012. View Article : Google Scholar : PubMed/NCBI
23	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
24	Chen K and Rajewsky N: The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet. 8:93–103. 2007. View Article : Google Scholar : PubMed/NCBI
25	Hui A, How C, Ito E and Liu FF: Micro-RNAs as diagnostic or prognostic markers in human epithelial malignancies. BMC Cancer. 11:5002011. View Article : Google Scholar : PubMed/NCBI
26	Yanaka Y, Muramatsu T, Uetake H, Kozaki K and Inazawa J: miR-544a induces epithelial-mesenchymal transition through the activation of WNT signaling pathway in gastric cancer. Carcinogenesis. 36:1363–1371. 2015. View Article : Google Scholar : PubMed/NCBI
27	Zhang X, Peng Y, Jin Z, Huang Q, Cheng Y, Liu Y, Feng X, Yang M, Huang Y, Zhao Z, et al: Integrated miRNA profiling and bioinformatics analyses reveal potential causative miRNAs in gastric adenocarcinoma. Oncotarget. 6:32878–32889. 2015.PubMed/NCBI
28	Blanco-Calvo M, Calvo L, Figueroa A, Haz-Conde M, Anton-Aparicio L and Valladares-Ayerbes M: Circulating microRNAs: Molecular microsensors in gastrointestinal cancer. Sensors (Basel). 12:9349–9362. 2012. View Article : Google Scholar
29	Dar AA, Majid S, de Semir D, Nosrati M, Bezrookove V and Kashani-Sabet M: miRNA-205 suppresses melanoma cell proliferation and induces senescence via regulation of E2F1 protein. J Biol Chem. 286:16606–16614. 2011. View Article : Google Scholar : PubMed/NCBI
30	Brabletz S and Brabletz T: The ZEB/miR-200 feedback loop - a motor of cellular plasticity in development and cancer? EMBO Rep. 11:670–677. 2010. View Article : Google Scholar : PubMed/NCBI
31	Gheldof A, Hulpiau P, van Roy F, De Craene B and Berx G: Evolutionary functional analysis and molecular regulation of the ZEB transcription factors. Cell Mol Life Sci. 69:2527–2541. 2012. View Article : Google Scholar : PubMed/NCBI
32	Arumugam T, Ramachandran V, Fournier KF, Wang H, Marquis L, Abbruzzese JL, Gallick GE, Logsdon CD, McConkey DJ and Choi W: Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 69:5820–5828. 2009. View Article : Google Scholar : PubMed/NCBI