MicroRNA-21 promotes proliferation, migration, and invasion of colorectal cancer, and tumor growth associated with down-regulation of sec23a expression.
MicroRNA-21 promotes proliferation, migration, and invasion of colorectal cancer, and tumor growth associated with down-regulation of sec23a expression.
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DOI：
10.1186/s12885-016-2628-z
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发表时间：
2016-08-05
期刊：
影响因子：
3.8
通讯作者：
Meng QH
中科院分区：
文献类型：
--
作者：
Li C;Zhao L;Chen Y;He T;Chen X;Mao J;Li C;Lyu J;Meng QH
MicroRNA-21（miR-21）在许多癌症中上调，包括结直肠癌（CRC）。然而，miR-21在CRC中的功能及其作用机制仍不清楚。在分析了CRC细胞系中miR-21和Sec 23 A的表达后，我们用含有miR-21抑制剂的质粒转染了最高表达miR-21的细胞系SW-480，并用含有miR-21抑制剂的质粒转染了最低表达miR-21的细胞系DLD-1。模拟物并测量了对Sec 23 A表达以及对细胞增殖、迁移和侵袭的影响。我们还评估了敲低Sec 23 A对miR-21表达的影响及其对细胞增殖、迁移和侵袭的影响。最后，我们评估了miR-21在小鼠异种移植肿瘤模型中的作用。对这些小鼠的肿瘤组织进行免疫组织化学染色以检测Sec 23 A的表达。miR-21基因缺失抑制SW-480细胞的增殖、迁移和侵袭，而miR-21过表达促进DLD-1细胞的增殖、迁移和侵袭。抑制miR-21可增加SW-480细胞中Sec 23 A蛋白的表达，而过表达miR-21可显著抑制DLD-1细胞中Sec 23 A蛋白和Sec 23 A mRNA的表达。Sec 23 A的敲低增加了SW 480和DLD-1细胞中miR-21的表达及其增殖（仅DLD-1）、迁移和侵袭。过表达miR-21可促进BALB/c裸鼠肿瘤生长并抑制肿瘤Sec 23 A的表达。这些发现为miR-21在CRC中的分子功能提供了新的见解，这可能是一个潜在的有趣的靶点。
MicroRNA-21 (miR-21) is up-regulated in many cancers, including colorectal cancer (CRC). Nevertheless, the function of miR-21 in CRC and the mechanism underlying that function is still unclear. After analyzing the expression of miR-21 and Sec23A in CRC cell lines, we transfected the highest miR-21 expressing cell line, SW-480, with a plasmid containing an miR-21 inhibitor and the lowest miR-21 expressing cell line, DLD-1, with a plasmid containing an miR-21 mimic and measured the effects on the expression of Sec23A and on cell proliferation, migration, and invasion. We also evaluated the effect of knocking down Sec23A on miR-21 expression and its effects on cell proliferation, migration, and invasion. Finally, we assessed the effect of miR-21 in a xenograft tumor model in mice. Tumor tissues from these mice were subjected to immunohistochemical staining to detect the expression of Sec23A. Genetic deletion of miR-21 suppressed the proliferation, migration, and invasion of SW-480 cells, while over-expression of miR-21 promoted proliferation, migration, and invasion of DLD-1 cells. Inhibition of miR-21 increased the expression of Sec23A protein in SW-480 cells while over-expression of miR-21 significantly suppressed the expression of Sec23A protein and Sec23A mRNA in DLD-1 cells. Knockdown of Sec23A increased the expression of miR-21 in SW480 and DLD-1 cells and their proliferation (DLD-1 only), migration, and invasion. Over-expression of miR-21 promoted tumor growth in BALB/c nude mice and suppressed tumor expression of Sec23A. These findings provide novel insight into the molecular functions of miR-21 in CRC, which may serve as a potential interesting target.