Bao Jing, Li Xiaofeng, Li Yuhuan, Huang Cheng, Meng Xiaoming, Li Jun
Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.
The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China.
Front Pharmacol. 2020 Jan 22;10:1545. doi: 10.3389/fphar.2019.01545. eCollection 2019.
MicroRNA-141-5p (miR-141-5p), an important member of the miR-200 family, has been reported to be involved in cellular proliferation, migration, invasion, and drug resistance in different kinds of human malignant tumors. However, the role and function of miR-141-5p in chronic myeloid leukemia (CML) are unclear. In this current study, we found that the level of miR-141-5p was significantly decreased in peripheral blood cells from CML patients compared with normal blood cells and human leukemic cell line (K562 cells) compared with normal CD34 cells, but was remarkably elevated in patients after treatment with nilotinib or imatinib. Suppression of miR-141-5p promoted K562 cell proliferation and migration . As expected, overexpression of miR-141-5p weakened K562 cell proliferation, migration, and promoted cell apoptosis. A xenograft model in nude mice showed that overexpression of miR-141-5p markedly suppressed tumor growth . Mechanistic studies suggested that RAB32 was the potential target of miR-141-5p, and silencing of RAB32 suppressed the proliferation and migration of K562 cells and promoted cell apoptosis. Taken together, our study demonstrates that miR-141-5p plays an important role in the activation of K562 cells and may act as a tumor suppressor targeting RAB32 in the development of CML.
微小RNA-141-5p（miR-141-5p）是miR-200家族的重要成员，据报道它参与了多种人类恶性肿瘤的细胞增殖、迁移、侵袭和耐药过程。然而，miR-141-5p在慢性髓性白血病（CML）中的作用和功能尚不清楚。在本研究中，我们发现与正常血细胞相比，CML患者外周血细胞中miR-141-5p水平显著降低；与正常CD34细胞相比，人白血病细胞系（K562细胞）中miR-141-5p水平也显著降低，但在接受尼洛替尼或伊马替尼治疗后的患者中，miR-141-5p水平显著升高。抑制miR-141-5p可促进K562细胞增殖和迁移。正如预期的那样，miR-141-5p的过表达减弱了K562细胞的增殖和迁移，并促进细胞凋亡。裸鼠异种移植模型显示，miR-141-5p的过表达显著抑制肿瘤生长。机制研究表明，RAB32是miR-141-5p的潜在靶标，沉默RAB32可抑制K562细胞的增殖和迁移，并促进细胞凋亡。综上所述，我们的研究表明miR-141-5p在K562细胞激活中起重要作用，并且在CML发生发展过程中可能作为靶向RAB32的肿瘤抑制因子。
