LINC01287 通过 miR-4500/MAP3K13 通路促进结肠癌细胞的增殖、迁移、侵袭和 EMT。
LINC01287 facilitates proliferation, migration, invasion and EMT of colon cancer cells via miR-4500/MAP3K13 pathway.
机构信息
Department of General Surgery, First Affiliated Hospital of China Medical University, NO. 155 Nanjingbei Road, Heping District, Shenyang, 110001, Liaoning, China.
Department of Interventional Radiology, Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
出版信息
BMC Cancer. 2021 Jul 6;21(1):782. doi: 10.1186/s12885-021-08528-7.
BACKGROUND
Accumulated studies indicate that aberrant expression of long noncoding RNAs (lncRNAs) is associated with tumorigenesis and progression of colon cancer. In the present study, long intergenic non-protein coding RNA 1287 (LINC01287) was identified to up-regulate in colon cancer by transcriptome RNA-sequencing, but the exact function remained unclear.
METHODS
Transcriptome RNA-sequencing was conducted to identify dysregulated lncRNAs. Expression of LINC01287 was evaluated by real-time quantitative PCR. The downstream targets of LINC01287 and miR-4500 were verified by luciferase reporter assay, pull down assay and western blot. The potential functions of LINC01287 were evaluated by cell viability assay, colony formation assay, soft agar assay, flow cytometry, transwell migration and invasion assay, and tumor xenograft growth in colon cancer cells.
RESULTS
Our results indicated that LINC01287 was up-regulated in colon cancer patients. High LINC01287 expression was associated with advanced TNM stage, lymph node metastasis, distant metastasis and shorter overall survival. Knockdown of LINC01287 inhibited cell growth, colony formation in plates and soft agar, transwell cell migration and invasion, and epithelial-mesenchymal transition (EMT) of colon cancer cells, while LINC01287 overexpression had contrary effects. In addition, LINC01287 mediated MAP3K13 expression by sponging miR-4500, thus promoted NF-κB p65 phosphorylation. Restored MAP3K13 expression or miR-4500 knockdown partially abrogated the effects of silencing LINC01287 in colon cancer cells.
CONCLUSION
Our findings demonstrated that the LINC01287/miR-4500/MAP3K13 axis promoted progression of colon cancer. Therefore, LINC01287 might be a potential therapeutic target and prognostic marker for colon cancer patients.
背景
累积研究表明，长链非编码 RNA（lncRNAs）的异常表达与结肠癌的发生和进展有关。在本研究中，通过转录组 RNA 测序发现长基因间非蛋白编码 RNA 1287（LINC01287）在结肠癌中上调，但确切功能尚不清楚。
方法
通过转录组 RNA 测序鉴定失调的 lncRNAs。实时定量 PCR 评估 LINC01287 的表达。通过荧光素酶报告基因检测、下拉实验和 Western blot 验证 LINC01287 和 miR-4500 的下游靶标。通过细胞活力测定、集落形成测定、软琼脂测定、流式细胞术、Transwell 迁移和侵袭测定以及结肠癌细胞的肿瘤异种移植生长评估 LINC01287 的潜在功能。
结果
我们的结果表明，LINC01287 在结肠癌患者中上调。高 LINC01287 表达与较晚的 TNM 分期、淋巴结转移、远处转移和较短的总生存期相关。敲低 LINC01287 抑制结肠癌细胞的生长、平板和软琼脂集落形成、Transwell 细胞迁移和侵袭以及上皮-间充质转化（EMT），而 LINC01287 过表达则有相反的作用。此外，LINC01287 通过海绵吸附 miR-4500 介导 MAP3K13 的表达，从而促进 NF-κB p65 磷酸化。恢复 MAP3K13 的表达或 miR-4500 的敲低部分消除了沉默 LINC01287 在结肠癌细胞中的作用。
结论
我们的研究结果表明，LINC01287/miR-4500/MAP3K13 轴促进了结肠癌的进展。因此，LINC01287 可能是结肠癌患者潜在的治疗靶点和预后标志物。
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