Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
The Key Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Cell Biochem. 2018 Nov;119(10):8138-8145. doi: 10.1002/jcb.26767. Epub 2018 Jun 19.
miR-30d has been shown to play pivotal roles in cancer development, and has the potential to act as a diagnostic biomarker and therapeutic target in breast cancer. However, the specific function and molecular mechanism of miR-30d in breast cancer cell growth and metastasis is still unknown. The present study seeks to shed light on the potential contribution of the MiR-30d-KLF-11-STAT3 pathway in breast cancer. The results revealed that miR-30d levels were markedly increased in the breast cancer cell lines BT474, MDA-MB-231, HCC197, and MDA-MB-468 compared with the non-tumor mammary gland MCF10A cell line. Furthermore, the miR-30d mimic increased BT474 and MDA-MB-231 breast cancer cell survival, inhibited apoptosis and increased Bcl-2 expression, whilst inhibited Bax protein levels. miR-30d mimics promote BT474 and MDA-MB-231 cell migration, invasion, and mediate the EMT phenotype. However, miR-30d inhibitors reverse all of the effects of miR-30d mimics on breast cancer cell biology. Also, we observed that KLF-11 is a direct target of miR-30d and KLF-11 and pSTAT3 expression are determined by miR-30d. Finally, the results suggest that miR-30d plays essential roles in breast cancer cells in a manner that is dependent on the levels of KLF-1 and pSTAT3. In summary, miR-30d appears to be a novel diagnostic biomarker and treatment target in breast cancer.
miR-30d 在癌症发展中发挥着关键作用，有可能成为乳腺癌的诊断生物标志物和治疗靶点。然而，miR-30d 在乳腺癌细胞生长和转移中的具体功能和分子机制尚不清楚。本研究旨在探讨 MiR-30d-KLF-11-STAT3 通路在乳腺癌中的潜在作用。结果显示，与非肿瘤乳腺 MCF10A 细胞系相比，乳腺癌细胞系 BT474、MDA-MB-231、HCC197 和 MDA-MB-468 中 miR-30d 水平明显升高。此外，miR-30d 模拟物增加了 BT474 和 MDA-MB-231 乳腺癌细胞的存活，抑制了细胞凋亡并增加了 Bcl-2 的表达，同时抑制了 Bax 蛋白水平。miR-30d 模拟物促进了 BT474 和 MDA-MB-231 乳腺癌细胞的迁移和侵袭，并介导 EMT 表型。然而，miR-30d 抑制剂逆转了 miR-30d 模拟物对乳腺癌细胞生物学的所有影响。此外，我们观察到 KLF-11 是 miR-30d 的直接靶标，KLF-11 和 pSTAT3 的表达受 miR-30d 调控。最后，结果表明 miR-30d 以依赖于 KLF-1 和 pSTAT3 水平的方式在乳腺癌细胞中发挥重要作用。综上所述，miR-30d 似乎是乳腺癌的一种新的诊断生物标志物和治疗靶点。
