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1、ORIGINAL ARTICLE—ALIMENTARY TRACTDown-regulation of miR-141 in gastric cancer and its involvement in cell growthYing Du Æ Yanjun Xu Æ Ling Ding Æ Haomi Yao Æ Hong Yu Æ Tianhua Zhou Æ Jianmin
2、 SiReceived: 18 August 2008 / Accepted: 28 January 2009 / Published online: 11 April 2009 ? Springer 2009Abstract Purpose Human microRNA-141 (miR-141), a member of the miR-200 family, has been reported to be associated w
3、ith various human malignancies. However, it remains unknown whether miR-141 is involved in the pathogenesis of gastric cancer. Therefore, we examined the expression of miR-141 in gastric cancer tissues and the effect of
4、miR- 141 overexpression on cancer cell proliferation. Methods The expression level of miR-141 in 35 pair- matched gastric neoplastic and adjacent non-neoplastic tissues, and in 5 gastric cancer cell lines were examined b
5、y quantitative real-time PCR. The growth of MGC-803 cells transfected with miRNA precursor was examined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazoliumbro- mide) assay. Results MiR-141 was significantly dow
6、n-regulated in 80% (28/35) of primary gastric cancer tissues compared with pair-matched adjacent non-tumor tissues (P \ 0.01). The expression of miR-141 was also found to be substan- tially reduced in several human gastr
7、ic cancer cell lines such as MGC-803, HGC-27, SGC-7901 and BGC-823cells. Overexpression of miR-141 with its precursors sig- nificantly inhibited the proliferation of gastric cancer cells. Conclusions These results sugges
8、t that miR-141 may be involved in the development of gastric cancer through its inhibitory effect on cell proliferation.Keywords MiR-141 ? Gastric cancer ? MGC-803 cell ? Cell proliferationIntroductionMicroRNAs (miRNAs),
9、 a new class of endogenous, noncoding and single-stranded RNAs, were recently discovered in both animals and plants. They trigger trans- lational repression and/or mRNA degradation mostly through complementary binding to
10、 the 30-untranslated regions of target mRNAs. Studies have shown that miR- NAs can regulate a wide array of biological processes such as cell proliferation, differentiation, and apoptosis [1]. Accumulating evidence sugge
11、sts that alterations of miR- NAs expression may play various roles in the pathogenesis of many human cancers [2, 3]. Some miRNAs has been shown to possess oncogenic or tumor suppressor activity [4]. High-throughput techn
12、iques have been used to screen miRNAs differentially expressed between human nonmalignant and malignant samples, and a number of miRNAs deregulated in numerous human tumors were found, including lung, breast, liver, esop
13、ha- geal and prostate cancers [5–9]. Among these miRNAs, miR-141, a member of the miR-200 family, is over- expressed in ovarian and colorectal cancers [10, 11] and down-regulated in prostate, hepatocellular, and renal ce
14、ll carcinoma [5, 9, 12], raising a controversial issue about the role of miR-141 in cancer progression.Electronic supplementary material The online version of this article (doi:10.1007/s00535-009-0037-7) contains supplem
15、entary material, which is available to authorized users.Y. Du ? H. Yu ? J. Si ( P \ 0.01). Substantially reduced expres- sions of miR-141 were found in both intestinal-type(1.7-fold; n = 23; Fig. 1b; P \ 0.05) and diffus
16、e-type gas- tric cancers (3.0-fold; n = 9; Fig. 1c; P \ 0.01).The expression of miR-141 in cell lines derived from gastric cancerTo confirm the association between miR-141 expression and gastric cancer, we detected miR-1
17、41 expression inFig. 1 The expression of miR-141 in gastric cancer. Quantification of miR-141 was measured by TaqMan real-time PCR. All data of fold change were transformed to log2 values. a Relative expression of miR-14
18、1 in 35 primary gastric cancer tissues compared with their pair-matched adjacent non-tumor tissues. b Relative expression of miR-141 in 23 tissues with intestinal-type adenocarcinoma relative to their pair-matched adjace
19、nt nonmalignant tissues. c Relative expres- sion of miR-141 in 9 diffuse-type adenocarcinoma tissues compared with their pair-matched adjacent non-tumor tissues. The pathological features of representative intestinal-typ
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