MicroRNA-26b represses colon cancer cell proliferation by inhibiting lymphoid enhancer factor 1 expression.
MicroRNA-26b represses colon cancer cell proliferation by inhibiting lymphoid enhancer factor 1 expression.
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DOI：
10.1158/1535-7163.mct-13-1000
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发表时间：
2014-07
影响因子：
5.7
通讯作者：
Amendt BA
中科院分区：
文献类型：
--
作者：
Zhang Z;Kim K;Li X;Moreno M;Sharp T;Goodheart MJ;Safe S;Dupuy AJ;Amendt BA
微小RNA（miR）可作为癌基因和肿瘤抑制因子，一些miR通过调节多种细胞过程与癌症的发生和发展相关。miR - 26b在多种癌症和肿瘤中表达下调，并且miR - 26b直接靶向Lef - 1的3'非翻译区（3'UTR）并抑制内源性Lef - 1的表达。我们报道miR - 26b的表达通过调节结肠癌细胞中LEF - 1的表达与人类结肠癌相关。对多种结肠癌细胞系的分析显示miR - 26b和LEF - 1的表达呈负相关。正常人结肠细胞表达低水平的LEF - 1和高水平的miR - 26b，然而人类结肠癌细胞中miR - 26b表达降低，LEF - 1表达增加。我们证明miR - 26b的表达是结肠癌细胞增殖的强效抑制剂，并显著降低LEF - 1的表达。LEF - 1调控的基因细胞周期蛋白D1（Cyclin D1）和c - Myc被miR - 26b间接抑制，这与增殖减少一致。miR - 26b在SW480结肠癌细胞中的过表达也抑制了裸鼠体内的肿瘤生长，这是由于肿瘤生长减缓而非细胞凋亡。对人类结肠癌数据库的分析也证明了miR - 26b和LEF - 1表达之间的联系。c - Myc的表达与多种癌症相关，我们提出miR - 26b可能作为一种潜在的治疗剂，通过抑制LEF - 1对c - Myc和细胞周期蛋白D1表达的激活来减少癌细胞的增殖。
microRNAs (miR) can act as oncogenes and tumor suppressors and several miRs are associated with cancer development and progression through the modulation of multiple cellular processes. miR-26b is down regulated in several cancers and tumors and miR-26b directly targets the Lef-1 3'UTR and inhibits endogenous Lef-1 expression. We report that miR-26b expression is associated with human colon cancer through the regulation of LEF-1 expression in colon cancer cells. Analyses of multiple colon cancer cell lines revealed an inverse correlation between miR-26b and LEF-1 expression. Normal human colon cells express low levels of LEF-1 and high levels of miR-26b, however human colon cancer cells have decreased miR-26b expression and increased LEF-1 expression. We demonstrate that miR-26b expression is a potent inhibitor of colon cancer cell proliferation and significantly decreases LEF-1 expression. The LEF-1 regualted genes Cyclin D1 and c-Myc were indirectly repressed by miR-26b and this was consistent with decreased proliferation. miR-26b overexpression in SW480 colon cancer cells also inhibited tumor growth in nude mice and this was due to decreased tumor growth and not apoptosis. Analyses of human colon cancer databases also demonstrated a link between miR-26b and LEF-1 expression. c-Myc expression is associated with multiple cancers and we propose that miR-26b may act as a potential therapeutic agent in reducing cancer cell proliferation through repressing LEF-1 activation of c-Myc and Cyclin D1 expression.