Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, China.
Department of Dermatology, Renmin Hospital, Hubei University of Medicine, Shiyan, China.
Oral Dis. 2021 Oct;27(7):1678-1686. doi: 10.1111/odi.13706. Epub 2020 Nov 26.
Laryngeal cancer is a common type of head and neck malignancy. microRNA is implicated in the development and progression of various tumours. The present study aimed to explore the potential roles and mechanisms of miR-646 in laryngeal carcinoma cells. We detected the expression of miR-646 and observed that miR-646 was reduced in laryngeal cell lines. Subsequently, the proliferation, migration and invasion of TU212 and TU686 cells were evaluated using CCK-8 assays, cell proliferation ELISA BrdU and transwell assays after transfection with miR-646 mimic. Overexpression of miR-646 attenuated the proliferative and invasive abilities of TU212 and TU686 cells. Dual luciferase reporter assay confirmed that glutathione peroxidase 1 (GPX1) is a direct target of miR-646. Interestingly, restoration of GPX1 promoted cell proliferation and migration, and reversed the biological activities of miR-646 in cell proliferation and migration. It is worth noting that miR-646 overexpression blocked the activation of PI3K/AKT pathway, and this was partly abrogated by GPX1. 740Y-P, a PI3K agonist abolished the effects of miR-646 on cell proliferation and invasion. Taken together, miR-646 prohibited the proliferation and invasion of laryngeal carcinoma cells through the PI3K/AKT pathway via targeting GPX1.
喉癌是一种常见的头颈部恶性肿瘤。miRNA 参与了多种肿瘤的发生和发展。本研究旨在探讨 miR-646 在喉癌细胞中的潜在作用和机制。我们检测了 miR-646 的表达，发现其在喉癌细胞系中降低。随后，通过 CCK-8 测定、细胞增殖 ELISA BrdU 和 Transwell 测定，观察 miR-646 模拟物转染后 TU212 和 TU686 细胞的增殖、迁移和侵袭情况。miR-646 的过表达减弱了 TU212 和 TU686 细胞的增殖和侵袭能力。双荧光素酶报告基因检测证实，谷胱甘肽过氧化物酶 1（GPX1）是 miR-646 的直接靶标。有趣的是，GPX1 的恢复促进了细胞增殖和迁移，并逆转了 miR-646 在细胞增殖和迁移中的生物学活性。值得注意的是，miR-646 过表达阻断了 PI3K/AKT 通路的激活，而这部分被 GPX1 阻断。PI3K 激动剂 740Y-P 消除了 miR-646 对细胞增殖和侵袭的影响。综上所述，miR-646 通过靶向 GPX1 抑制 PI3K/AKT 通路，从而抑制喉癌细胞的增殖和侵袭。
