miR-17-5p 和 MKL-1 调节胃癌细胞的干细胞特性。
MiR-17-5p and MKL-1 modulate stem cell characteristics of gastric cancer cells.
机构信息
Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei, 430081, P.R. China.
Department of Medical Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Hubei, 430014, P.R. China.
出版信息
Int J Biol Sci. 2021 Jun 4;17(9):2278-2293. doi: 10.7150/ijbs.57338. eCollection 2021.
Effectively targeting cancer stem cells to treat cancer has great therapeutic prospects. However, the effect of microRNA miR-17/MKL-1 on gastric cancer stem cells has not been studied yet. This study preliminarily explored the mechanism of miR-17/MKL-1 in gastric cancer stem cells. Many previous reports have indicated that microRNA and EMT regulated cancer stem cell characteristics, and miR-17 and MKL-1 were involved as a critical gene in migration and invasion in the EMT pathway. Through RT-PCR, Western Blot, flow cytometry, immunofluorescence, sphere formation xenograft tumor assays and drug resistance, the role of miR-17-5p and MKL-1 on promoting stem cell-like properties of gastric cancer were verified . Next, MKL-1 targets CD44, EpCAM, and miR -17-5p promoter verified by luciferase assay and . Besides, the TCGA database analysis found that both miR-17-5p and MKL-1 increased in gastric cancer, and the prognostic survival of the MKL-1 high expression group was reduced. It is found that MKL-1 promotes expression by targeting miR-17, CD44 and EpCAM promoters. Besides, the TCGA database analysis found that both miR-17-5p and MKL-1 increased in gastric cancer, and the prognostic survival of the MKL-1 high expression group was reduced. These findings reveal new regulatory signaling pathways for gastric cancer stem cells, thus it give new insights on potential early diagnosis and/or molecular therapy for gastric cancer.
有效靶向癌症干细胞治疗癌症具有广阔的治疗前景。然而，miR-17/MKL-1 对胃癌干细胞的作用尚未得到研究。本研究初步探讨了 miR-17/MKL-1 在胃癌干细胞中的作用机制。许多先前的报告表明，microRNA 和 EMT 调节癌症干细胞特性，miR-17 和 MKL-1 作为 EMT 途径中迁移和侵袭的关键基因参与其中。通过 RT-PCR、Western Blot、流式细胞术、免疫荧光、球体形成异种移植肿瘤实验和耐药性实验，验证了 miR-17-5p 和 MKL-1 在促进胃癌干细胞样特性中的作用。接下来，通过荧光素酶报告实验和 Western Blot 验证了 MKL-1 靶向 CD44、EpCAM 和 miR-17-5p 启动子。此外，TCGA 数据库分析发现 miR-17-5p 和 MKL-1 在胃癌中均增加，MKL-1 高表达组的预后生存率降低。研究发现 MKL-1 通过靶向 miR-17、CD44 和 EpCAM 启动子促进表达。此外，TCGA 数据库分析发现 miR-17-5p 和 MKL-1 在胃癌中均增加，MKL-1 高表达组的预后生存率降低。这些发现揭示了胃癌干细胞新的调节信号通路，为胃癌的早期诊断和/或分子治疗提供了新的思路。
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