miR-543 inhibites cervical cancer growth and metastasis by targeting TRPM7
miR-543 inhibites cervical cancer growth and metastasis by targeting TRPM7
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DOI：
10.1016/j.cbi.2019.01.036
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发表时间：
2019-04-01
影响因子：
5.1
通讯作者：
Zhang, Jing
中科院分区：
文献类型：
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作者：
Liu, Xiaoying;Gan, Lu;Zhang, Jing
miR-543的失调在各种人类癌症中起着至关重要的作用。然而，miR-543参与宫颈癌（CC）进展的功能在很大程度上仍然未知。因此，本研究旨在探讨miR-543在人类CC中的潜在作用及其潜在机制。在本研究中，我们发现，与邻近的正常组织和细胞系相比，miR-543在69个CC组织样本和细胞系中显著下调。miR-543的降低与肿瘤大小较大、FIGO分期较晚、淋巴结转移等不良临床病理参数密切相关。在CC细胞系中，过表达miR-543在体外显著抑制细胞增殖、侵袭和迁移，引起细胞周期阻滞，促进细胞凋亡，在体内抑制肿瘤生长，而miR-543抑制剂则表现出相反的作用。双荧光素酶检测证实瞬时受体电位美拉他汀7 （TRPM7）的3′-非翻译区（UTR）是miR-543的直接结合位点。修复实验表明，TRPM7表达的恢复部分逆转了mir -543介导的CC细胞增殖和侵袭抑制。进一步的研究证实P13K/AKT和p38/MAPK信号参与了miR-543/TRPM7轴介导的CC进展。因此，这些发现证明了miR-543在CC进展中的抑瘤作用，可能作为CC诊断和治疗的潜在生物标志物。
Dysregulation of miR-543 has been implicated to play crucial roles in various human cancers. However, the function of miR-543 involved in cervical cancer (CC) progress remains largely unknown. Thus, this study aimed to explore the potential role of miR-543 and the underlying mechanisms in human CC. In this study, we found that miR-543 was significantly downregulated in 69 CC tissue samples and cell lines when compared to adjacent normal tissues and cell line. Decreased miR-543 was closely correlated with poor clinicopathological parameters including larger tumor size, late FIGO stage and lymph node metastasis. Overexpression of miR-543 in CC cell lines remarkably inhibited cell proliferation, invasion and migration, caused cell cycle arrest, promoted apoptosis in vitro, and suppressed tumor growth in vivo, whereas miR-543 inhibitor showed the opposite effect. Dual-luciferase assay validated that 3'-untranslated region (UTR) of transient receptor potential melastatin 7 (TRPM7) was a direct binding site of miR-543. Rescue experiments showed that restoration of TRPM7 expression partially reversed the miR-543-mediated inhibition of proliferation and invasion in CC cells. Further studies confirmed that P13K/AKT and p38/MAPK signaling was involved in miR-543/TRPM7 axis mediated CC progression. Thus, these findings demonstrated the tumor suppressor role of miR-543 on CC progression, which might serve as a potential biomarker for CC diagnosis and therapy.