MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation.
MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation.
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MicroRNA-148b 在胃癌中经常下调，并通过抑制细胞增殖发挥肿瘤抑制因子的作用
DOI：
10.1186/1476-4598-10-1
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发表时间：
2011-01-04
期刊：
影响因子：
37.3
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Song YX;Yue ZY;Wang ZN;Xu YY;Luo Y;Xu HM;Zhang X;Jiang L;Xing CZ;Zhang Y
研究背景MicroRNAs(MiRNAs)参与肿瘤的发生发展，作为肿瘤抑制基因或癌基因发挥作用。我们先前的研究表明miR-148A和miR-152在胃肠道肿瘤中显著下调。有趣的是，miR-148B与miR-148A和miR-152具有相同的“种子序列”。虽然已经观察到miR-148B在多种类型的癌症中的异常表达，但其病理生理作用及其与肿瘤发生的相关性仍然很大程度上是未知的。本研究的目的是阐明miR-148B在胃癌中的抑制作用的分子机制。结果实时定量RT-PCR法显示，在106例胃癌组织和4种胃癌细胞系中miR-148B的表达水平显著低于相应的非肿瘤组织。经M ann-Whitney U检验，miR-148B的表达与肿瘤大小有关(P=0.027)。体外培养的MGC-803、SGC-7901、BGC-823和AGS细胞的生长曲线和贴壁非依赖生长实验表明，miR-148B对细胞增殖有明显的抑制作用。在裸鼠身上的实验表明，miR-148B可以抑制体内的成瘤作用。通过荧光素酶活性测定和Western印迹分析，CCKBR被鉴定为miR-148B在细胞内的靶标。在49对胃癌组织中，CCKBR蛋白的表达与miR-148B的表达呈显著负相关(P=0.002，Spearman相关)。结论miR-148B靶向CCKBR，对抑制胃癌细胞生长有重要意义。MiR-148B可能成为一种潜在的胃癌生物标志物和治疗靶点。
BackgroundMicroRNAs (miRNAs) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Our previous studies have revealed that miR-148a and miR-152 are significantly down-regulated in gastrointestinal cancers. Interestingly, miR-148b has the same "seed sequences" as miR-148a and miR-152. Although aberrant expression of miR-148b has been observed in several types of cancer, its pathophysiologic role and relevance to tumorigenesis are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which miR-148b acts as a tumor suppressor in gastric cancer.ResultsWe showed significant down-regulation of miR-148b in 106 gastric cancer tissues and four gastric cancer cell lines, compared with their non-tumor counterparts by real-time RT-PCR.In situhybridization of ten cases confirmed an overt decrease in the level of miR-148b in gastric cancer tissues. Moreover, the expression of miR-148b was demonstrated to be associated with tumor size (P = 0.027) by a Mann-Whitney U test. We also found that miR-148b could inhibit cell proliferationin vitroby MTT assay, growth curves and an anchorage-independent growth assay in MGC-803, SGC-7901, BGC-823 and AGS cells. An experiment in nude mice revealed that miR-148b could suppress tumorigenicityin vivo. Using a luciferase activity assay and western blot, CCKBR was identified as a target of miR-148b in cells. Moreover, an obvious inverse correlation was observed between the expression of CCKBR protein and miR-148b in 49 pairs of tissues (P = 0.002, Spearman's correlation).ConclusionsThese findings provide important evidence that miR-148b targets CCKBR and is significant in suppressing gastric cancer cell growth. Maybe miR-148b would become a potential biomarker and therapeutic target against gastric cancer.
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影响因子：
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作者：
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通讯作者：
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