Expression levels of microRNA-375 in pancreatic cancer

Song,Shiduo; Zhou,Jian; He,Songbing; Zhu,Dongming; Zhang,Zixiang; Zhao,Hua; Wang,Yi; Li,Dechun

doi:10.3892/br.2013.88

Expression levels of microRNA-375 in pancreatic cancer

Authors:
- Shiduo Song
- Jian Zhou
- Songbing He
- Dongming Zhu
- Zixiang Zhang
- Hua Zhao
- Yi Wang
- Dechun Li
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: March 27, 2013 https://doi.org/10.3892/br.2013.88
Pages: 393-398

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Abstract

MicroRNAs (miRNAs) are small, non‑coding RNAs of endogenous origin that have been increasingly shown to have altered expressions in various cancer types. The expression levels of miR-375 have not been comprehensively investigated in pancreatic cancer. In this study, total RNA was extracted from 44 pairs of pancreatic cancer tissues and non‑tumor adjacent tissues, as well as from four pancreatic cancer cell lines, Panc-1, SW1990, BxpC3 and Patu8988. Following polyadenylation and reverse transcription, the expression levels of miR-375 were determined by real-time PCR and the difference in expression was calculated using the 2-∆∆Ct method. The correlation between the expression levels of miR‑375 and clinicopathological characteristics of pancreatic cancer was also assessed. miR-375 expression was frequently downregulated in the pancreatic cancer tissues compared to their non‑tumor counterparts (P<0.05; paired t-test). Moreover, a significantly low expression of miR-375 was found in the pancreatic cancer cell lines (Panc-1, P=0.016; SW1990, P=0.016; BxPC3, P=0.018; Patu8988, P=0.017; paired t-test). However, no significant correlations were observed between the low expression of miR-375 and parameters including gender, age, tumor size, tumor location and histological grade (P>0.05). The low expression of miR‑375 was correlated with pT stage, lymph node metastases and pTNM stage (P<0.05) (non‑parametric test; Mann-Whitney U test between 2 groups and Kruskal‑Wallis H test for ≥3 groups). In conclusion, miR-375 is potentially involved in the carcinogenesis of pancreatic cancers and serves as is a potential biomarker for pancreatic cancer.

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1	Lee RC, Feinbaum RL and Ambros V: The C. elegansheterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993.
2	Bushati N and Cohen SM: microRNA functions. Annu Rev Cell Dev Biol. 23:175–205. 2007. View Article : Google Scholar
3	Carthew RW and Sontheimer EJ: Origins and mechanisms of miRNAs and siRNAs. Cell. 136:642–655. 2009. View Article : Google Scholar : PubMed/NCBI
4	Zeng Y: Principles of micro-RNA production and maturation. Oncogene. 25:6156–6162. 2006. View Article : Google Scholar : PubMed/NCBI
5	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. 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	He L and Hannon GJ: MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI
8	Zaman MS, Chen Y, Deng G, et al: The functional significance of microRNA-145 in prostate cancer. Br J Cancer. 103:256–264. 2010. View Article : Google Scholar : PubMed/NCBI
9	Yu S, Lu Z, Liu C, et al: miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 70:6015–6025. 2010. View Article : Google Scholar : PubMed/NCBI
10	Schickel R, Park SM, Murmann AE and Peter ME: miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1. Mol Cell. 38:908–915. 2010. View Article : Google Scholar : PubMed/NCBI
11	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar
12	Mori Y, Ishiguro H, Kuwabara Y, et al: MicroRNA-21 induces cell proliferation and invasion in esophageal squamous cell carcinoma. Mol Med Rep. 2:235–239. 2009.PubMed/NCBI
13	Takamizawa J, Konishi H, Yanagisawa K, et al: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64:3753–3756. 2004. View Article : Google Scholar : PubMed/NCBI
14	Iorio MV, Ferracin M, Liu CG, et al: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65:7065–7070. 2005. View Article : Google Scholar : PubMed/NCBI
15	Ikenaga N, Ohuchida K, Mizumoto K, et al: MicroRNA-203 expression as a new prognostic marker of pancreatic adenocarcinoma. Ann Surg Oncol. 17:3120–3128. 2010. View Article : Google Scholar : PubMed/NCBI
16	Murakami Y, Yasuda T, Saigo K, et al: Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene. 25:2537–2545. 2006. View Article : Google Scholar : PubMed/NCBI
17	Dai X, Chiang Y, Wang Z, et al: Expression levels of microRNA-375 in colorectal carcinoma. Mol Med Rep. 5:1299–1304. 2012.PubMed/NCBI
18	Ding L, Xu Y, Zhang W, et al: MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2. Cell Res. 20:784–793. 2010. View Article : Google Scholar : PubMed/NCBI
19	Calin GA, Sevignani C, Dumitru CD, et al: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar
20	Li D, Xie K, Wolff R and Abbruzzese JL: Pancreatic cancer. Lancet. 363:1049–1057. 2004. View Article : Google Scholar
21	Guo X and Cui Z: Current diagnosis and treatment of pancreatic cancer in China. Pancreas. 31:13–22. 2005. View Article : Google Scholar : PubMed/NCBI
22	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar
23	Szafranska AE, Davison TS, John J, et al: MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene. 26:4442–4452. 2007. View Article : Google Scholar
24	Bloomston M, Frankel WL, Petrocca F, et al: MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 297:1901–1908. 2007. View Article : Google Scholar
25	Park JY, Helm J, Coppola D, Kim D, Malafa M and Kim SJ: MicroRNAs in pancreatic ductal adenocarcinoma. World J Gastroenterol. 17:817–827. 2011. View Article : Google Scholar : PubMed/NCBI
26	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
27	Lee EJ, Gusev Y, Jiang J, et al: Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 120:1046–1054. 2007. View Article : Google Scholar : PubMed/NCBI
28	Zhang Y, Li M, Wang H, et al: Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis. World J Surg. 33:698–709. 2009. View Article : Google Scholar : PubMed/NCBI
29	Poy MN, Hausser J, Trajkovski M, et al: miR-375 maintains normal pancreatic alpha- and beta-cell mass. Proc Natl Acad Sci USA. 106:5813–5818. 2009. View Article : Google Scholar : PubMed/NCBI
30	El Ouaamari A, Baroukh N, Martens GA, Lebrun P, Pipeleers D and van Obberghen E: miR-375 targets 3′-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells. Diabetes. 57:2708–2717. 2008.
31	Tsukamoto Y, Nakada C, Noguchi T, et al: MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta. Cancer Res. 70:2339–2349. 2010. View Article : Google Scholar : PubMed/NCBI
32	Li X, Lin R and Li J: Epigenetic silencing of microRNA-375 regulates PDK1 expression in esophageal cancer. Dig Dis Sci. 56:2849–2856. 2011. View Article : Google Scholar : PubMed/NCBI
33	Kozma SC and Thomas G: Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K. Bioessays. 24:65–71. 2002. View Article : Google Scholar : PubMed/NCBI
34	Mora A, Komander D, van Aalten DM and Alessi DR: PDK1, the master regulator of AGC kinase signal transduction. Semin Cell Dev Biol. 15:161–170. 2004. View Article : Google Scholar : PubMed/NCBI
35	Westmoreland JJ, Wang Q, Bouzaffour M, Baker SJ and Sosa-Pineda B: Pdk1 activity controls proliferation, survival, and growth of developing pancreatic cells. Dev Biol. 334:285–298. 2009. View Article : Google Scholar : PubMed/NCBI
36	Storz P and Toker A: 3′-phosphoinositide-dependent kinase-1 (PDK-1) in PI 3-kinase signaling. Front Biosci. 7:d886–d902. 2002.
37	Ladeiro Y, Couchy G, Balabaud C, et al: MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology. 47:1955–1963. 2008. View Article : Google Scholar : PubMed/NCBI
38	Avissar M, Christensen BC, Kelsey KT and Marsit CJ: MicroRNA expression ratio is predictive of head and neck squamous cell carcinoma. Clin Cancer Res. 15:2850–2855. 2009. View Article : Google Scholar : PubMed/NCBI
39	Poy MN, Eliasson L, Krutzfeldt J, et al: A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 432:226–230. 2004. View Article : Google Scholar : PubMed/NCBI
40	Liu AM, Poon RT and Luk JM: MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties. Biochem Biophys Res Commun. 394:623–627. 2010. View Article : Google Scholar : PubMed/NCBI