Department of Gynecology, Shaanxi Provincial People's Hospital, 710068, Shaanxi, China.
Department of Gynecology, Shaanxi Provincial People's Hospital, 710068, Shaanxi, China.
Chem Biol Interact. 2019 Apr 1;302:83-92. doi: 10.1016/j.cbi.2019.01.036. Epub 2019 Jan 30.
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.
miR-543 的失调已被证明在各种人类癌症中发挥着关键作用。然而，miR-543 在宫颈癌（CC）进展中所涉及的功能在很大程度上仍是未知的。因此，本研究旨在探讨 miR-543 在人 CC 中的潜在作用及其潜在机制。在本研究中，我们发现与相邻正常组织和细胞系相比，69 个 CC 组织样本和细胞系中的 miR-543 显著下调。miR-543 的减少与较差的临床病理参数密切相关，包括较大的肿瘤大小、晚期 FIGO 分期和淋巴结转移。在 CC 细胞系中过表达 miR-543 可显著抑制细胞增殖、侵袭和迁移，导致细胞周期停滞，促进体外细胞凋亡，并抑制体内肿瘤生长，而 miR-543 抑制剂则表现出相反的效果。双荧光素酶报告基因实验验证了瞬时受体电位 melastatin 7（TRPM7）的 3'-非翻译区（UTR）是 miR-543 的直接结合位点。挽救实验表明，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作用。进一步的研究证实，PI3K/AKT 和 p38/MAPK 信号通路参与了 miR-543/TRPM7 轴介导的 CC 进展。因此，这些发现表明 miR-543 在 CC 进展中具有肿瘤抑制作用，可作为 CC 诊断和治疗的潜在生物标志物。
