CD44v6 Targeted by miR-193b-5p in the Coding Region Modulates the Migration and Invasion of Breast Cancer Cells
CD44v6 Targeted by miR-193b-5p in the Coding Region Modulates the Migration and Invasion of Breast Cancer Cells
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编码区 miR-193b-5p 靶向的 CD44v6 调节乳腺癌细胞的迁移和侵袭
DOI：
10.7150/jca.35067
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Gao, Feng
中科院分区：
文献类型：
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作者：
Hu, Song;Cao, Manlin;Gao, Feng
此前的研究表明，含有变异外显子v6（CD44v6）的CD44在许多癌症中高表达，并与肿瘤转移相关。然而，CD44v6在乳腺癌中调控模式的详细机制仍不清楚。在这里，我们发现与低侵袭性乳腺癌细胞系相比，CD44v6 在侵袭性乳腺癌细胞系中显着上调。 CD44v6 下调可抑制细胞迁移和侵袭。 MiRWalk 和 RNAhybrid 软件揭示 miR-193b-5p 通过与外显子 v6 区域结合而成为靶向 CD44v6 的 miRNA。我们发现miR-193b-5p的过表达抑制了Hs-578t和BT-549细胞的迁移和侵袭，这可以通过恢复CD44v6的表达来挽救。接下来，我们确定了 miR-193b-5p 作为乳腺癌体外生物标志物的潜力。血清样本取自 58 名乳腺癌患者、36 名良性疾病患者和 58 名年龄匹配的无癌症对照者。结果显示，乳腺癌患者血清中miR-193b-5p的表达显着低于对照组，并且可以区分癌症和无癌样本。 miR-193b-5p的受试者工作特征曲线下面积（ROC）为0.762（95%置信区间：0.674-0.851），高于癌胚抗原（CEA）和癌抗原15-3（CA15-3）。与CEA和CA15-3组合相比，miR-193b-5p与CEA或CA15-3组合可以提高诊断效率。综上所述，我们的结果表明，miR-193b-5p 可以通过靶向乳腺癌中的 CD44v6 发挥肿瘤抑制 miRNA 的作用，并且血清 miR-193b-5p 可以作为乳腺癌诊断的生物标志物。
Previous studies have shown that CD44 containing variant exon v6 (CD44v6) is highly expressed in many cancers and is related to tumor metastasis. However, the detailed mechanism of the regulatory pattern of CD44v6 in breast cancer remains unclear. Here, we found that CD44v6 was significantly upregulated in invasive breast cancer cell lines compared with low-invasive breast cancer cell lines. Cell migration and invasion could be suppressed by CD44v6 downregulation. MiRWalk and RNAhybrid software revealed miR-193b-5p as a miRNA targeting CD44v6 by binding to the exon v6 region. We found that the overexpression of miR-193b-5p inhibited the migration and invasion of Hs-578t and BT-549 cells, which could be rescued by restoring the expression of CD44v6. Next, we determined the potential of miR-193b-5p as an in vitro biomarker for breast cancer. Serum samples were obtained from 58 breast cancer patients, 36 patients with benign disease and 58 age-matched cancer-free controls. The results showed that the expression of miR-193b-5p in the serum was significantly lower in breast cancer patients than in controls and could distinguish cancer from cancer-free samples. The area under the receiver operating characteristic curve (ROC) for miR-193b-5p was 0.762(95% confidence interval: 0.674-0.851), which was higher than that of carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3). Combining miR-193b-5p with CEA or CA15-3 could improve the diagnostic efficiency compared with the CEA and CA15-3 combination. Taken together, our results suggest that miR-193b-5p could function as a tumor-suppressive miRNA by targeting CD44v6 in breast cancer and that serum miR-193b-5p may serve as a biomarker for breast cancer diagnosis.