Characterization of microRNA expression in serous ovarian carcinoma

Li,Yanhong; Yao,Li; Liu,Fei; Hong,Jia; Chen,Lin; Zhang,Beilei; Zhang,Wei

doi:10.3892/ijmm.2014.1813

Characterization of microRNA expression in serous ovarian carcinoma

Authors:
- Yanhong Li
- Li Yao
- Fei Liu
- Jia Hong
- Lin Chen
- Beilei Zhang
- Wei Zhang
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Affiliations: Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China, The Helmholtz Sino‑German Research Laboratory for Cancer, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
Published online on: June 17, 2014 https://doi.org/10.3892/ijmm.2014.1813
Pages: 491-498

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Abstract

Serous ovarian cancer is a major gynecologic malignancy with a poor 5‑year survival rate. However, little is known regarding the behavior and genetics of ovarian tumorigenesis. MicroRNAs (miRNAs) have been shown to be dysregulated in ovarian carcinomas. To assess the miRNA expression profiles in serous ovarian cancer, we defined the patterns of miRNA expression in 100 formalin‑fixed, paraffin‑embedded ovarian cancer tissues blocks as well as 50 corresponding normal oviduct tissues using miRNA microarray. MiRNA expression profiling showed that 63 miRNAs were downregulated and 43 miRNAs were upregulated in serous ovarian cancer tissues compared with control tissues. The expression of five dysregulated miRNAs was validated using quantitative polymerase chain reaction (RT‑qPCR). GO term and pathway analysis revealed that the biological process of the cell cycle was significantly enriched and the MAPK signaling pathway was highly involved in the progression of ovarian cancer. The results suggested that the aberrant expression of miRNAs is involved in ovarian carcinogenesis and thus these miRNAs may function as diagnostic and prognostic biomarkers.

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1	Permuth-Wey J and Sellers TA: Epidemiology of ovarian cancer. Methods Mol Biol. 472:413–437. 2009. View Article : Google Scholar
2	Seidman JD and Kurman RJ: Pathology of ovarian carcinoma. Hematol Oncol Clin North Am. 17:909–925. vii2003. View Article : Google Scholar : PubMed/NCBI
3	Shih IeM and Kurman RJ: Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 164:1511–1518. 2004. View Article : Google Scholar : PubMed/NCBI
4	Seidman JD, Horkayne-Szakaly I, Haiba M, Boice CR, Kurman RJ and Ronnett BM: The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin. Int J Gynecol Pathol. 23:41–44. 2004. View Article : Google Scholar : PubMed/NCBI
5	Levanon K, Crum C and Drapkin R: New insights into the pathogenesis of serous ovarian cancer and its clinical impact. J Clin Oncol. 26:5284–5293. 2008. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
7	Wang F, Niu G, Chen X and Cao F: Molecular imaging of microRNAs. Eur J Nucl Med Mol Imaging. 38:1572–1579. 2011. View Article : Google Scholar : PubMed/NCBI
8	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
9	Wang F, Fu XD, Zhou Y and Zhang Y: Down-regulation of the cyclin E1 oncogene expression by microRNA-16–1 induces cell cycle arrest in human cancer cells. BMB Rep. 42:725–730. 2009.PubMed/NCBI
10	Wang F, Song X, Li X, et al: Noninvasive visualization of microRNA-16 in the chemoresistance of gastric cancer using a dual reporter gene imaging system. PLoS One. 8:e617922013. View Article : Google Scholar : PubMed/NCBI
11	Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM and Cohn DE: The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol. 112:55–59. 2009. View Article : Google Scholar : PubMed/NCBI
12	Yu SL, Chen HY, Chang GC, et al: MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 13:48–57. 2008. View Article : Google Scholar : PubMed/NCBI
13	Zaman MS, Maher DM, Khan S, Jaggi M and Chauhan SC: Current status and implications of microRNAs in ovarian cancer diagnosis and therapy. J Ovarian Res. 5:442012. View Article : Google Scholar
14	Zhang L, Volinia S, Bonome T, et al: Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci USA. 105:7004–7009. 2008. View Article : Google Scholar : PubMed/NCBI
15	Iorio MV, Visone R, Di Leva G, et al: MicroRNA signatures in human ovarian cancer. Cancer Res. 67:8699–8707. 2007. View Article : Google Scholar : PubMed/NCBI
16	Nam EJ, Yoon H, Kim SW, et al: MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res. 14:2690–2695. 2008. View Article : Google Scholar : PubMed/NCBI
17	Gallagher MF, Flavin RJ, Elbaruni SA, et al: Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients. J Ovarian Res. 2:192009. View Article : Google Scholar : PubMed/NCBI
18	Wyman SK, Parkin RK, Mitchell PS, et al: Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries. PLoS One. 4:e53112009. View Article : Google Scholar : PubMed/NCBI
19	Laios A, O’Toole S, Flavin R, et al: Potential role of miR-9 and miR-223 in recurrent ovarian cancer. Mol Cancer. 7:352008. View Article : Google Scholar : PubMed/NCBI
20	Eitan R, Kushnir M, Lithwick-Yanai G, et al: Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients. Gynecol Oncol. 114:253–259. 2009. View Article : Google Scholar : PubMed/NCBI
21	Yang N, Kaur S, Volinia S, et al: MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res. 68:10307–10314. 2008. View Article : Google Scholar : PubMed/NCBI
22	Mezzanzanica D, Bagnoli M, De Cecco L, Valeri B and Canevari S: Role of microRNAs in ovarian cancer pathogenesis and potential clinical implications. Int J Biochem Cell Biol. 42:1262–1272. 2010. View Article : Google Scholar : PubMed/NCBI
23	Kunej T, Godnic I, Ferdin J, Horvat S, Dovc P and Calin GA: Epigenetic regulation of microRNAs in cancer: an integrated review of literature. Mutat Res. 717:77–84. 2011. View Article : Google Scholar : PubMed/NCBI
24	Xiao F, Zuo Z, Cai G, Kang S, Gao X and Li T: miRecords: an integrated resource for microRNA-target interactions. Nucleic Acids Res. 37:D105–D110. 2009.PubMed/NCBI
25	Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009.PubMed/NCBI
26	Vlachos IS, Kostoulas N, Vergoulis T, et al: DIANA miRPath v. 20: investigating the combinatorial effect of microRNAs in pathways. Nucleic Acids Res. 40:W498–W504. 2012. View Article : Google Scholar : PubMed/NCBI
27	Suh KS, Park SW, Castro A, et al: Ovarian cancer biomarkers for molecular biosensors and translational medicine. Expert Rev Mol Diagn. 10:1069–1083. 2010. View Article : Google Scholar : PubMed/NCBI
28	Kriplani D and Patel MM: Immunohistochemistry: a diagnostic aid in differentiating primary epithelial ovarian tumors and tumors metastatic to the ovary. South Asian J Cancer. 2:254–258. 2013. View Article : Google Scholar : PubMed/NCBI
29	Muraoka T, Soh J, Toyooka S, et al: The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma. Lung Cancer. 82:485–490. 2013. View Article : Google Scholar : PubMed/NCBI
30	Nadal E, Chen G, Gallegos M, et al: Epigenetic inactivation of microRNA-34b/c predicts poor disease-free survival in early-stage lung adenocarcinoma. Clin Cancer Res. 19:6842–6852. 2013. View Article : Google Scholar : PubMed/NCBI
31	Suzuki R, Yamamoto E, Nojima M, et al: Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk. J Gastroenterol. Aug 13–2013.(Epub ahead of print).
32	He XX, Chang Y, Meng FY, et al: MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. Oncogene. 31:3357–3369. 2012. View Article : Google Scholar
33	Kong KL, Kwong DL, Chan TH, et al: MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor. Gut. 61:33–42. 2012. View Article : Google Scholar : PubMed/NCBI
34	Fu X, Han Y, Wu Y, et al: Prognostic role of microRNA-21 in various carcinomas: a systematic review and meta-analysis. Eur J Clin Invest. 41:1245–1253. 2011. View Article : Google Scholar : PubMed/NCBI
35	Yu X, Song H, Xia T, et al: Growth inhibitory effects of three miR-129 family members on gastric cancer. Gene. 532:87–93. 2013. View Article : Google Scholar : PubMed/NCBI
36	Karaayvaz M, Zhai H and Ju J: miR-129 promotes apoptosis and enhances chemosensitivity to 5-fluorouracil in colorectal cancer. Cell Death Dis. 4:e6592013. View Article : Google Scholar : PubMed/NCBI
37	Liu Y, Hei Y, Shu Q, et al: VCP/p97, down-regulated by microRNA-129–5p, could regulate the progression of hepatocellular carcinoma. PLoS One. 7:e358002012.PubMed/NCBI
38	Bray I, Tivnan A, Bryan K, et al: MicroRNA-542–5p as a novel tumor suppressor in neuroblastoma. Cancer Lett. 303:56–64. 2011.
39	Yamamoto S, Inoue J, Kawano T, Kozaki K, Omura K and Inazawa J: The impact of mirna-based molecular diagnostics and treatment of NRF2-stabilized tumors. Mol Cancer Res. 12:58–68. 2014. View Article : Google Scholar : PubMed/NCBI
40	Wu K, Hu G, He X, et al: MicroRNA-424–5p suppresses the expression of SOCS6 in pancreatic cancer. Pathol Oncol Res. 19:739–748. 2013.
41	Liang LH and He XH: Macro-management of microRNAs in cell cycle progression of tumor cells and its implications in anti-cancer therapy. Acta Pharmacol Sin. 32:1311–1320. 2011. View Article : Google Scholar : PubMed/NCBI
42	Makker A, Goel MM, Das V and Agarwal A: PI3K-Akt-mTOR and MAPK signaling pathways in polycystic ovarian syndrome, uterine leiomyomas and endometriosis: an update. Gynecol Endocrinol. 28:175–181. 2012. View Article : Google Scholar : PubMed/NCBI
43	Nilsson EE and Skinner MK: Role of transforming growth factor beta in ovarian surface epithelium biology and ovarian cancer. Reprod Biomed Online. 5:254–258. 2002. View Article : Google Scholar : PubMed/NCBI
44	Slaby O, Svoboda M, Fabian P, et al: Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 72:397–402. 2007. View Article : Google Scholar : PubMed/NCBI