Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan, China.
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan, China.
Pathol Res Pract. 2022 Aug;236:153912. doi: 10.1016/j.prp.2022.153912. Epub 2022 Apr 29.
Laryngeal cancer (LC), with a relatively rare diagnosis, is a primary malignancy originating from laryngeal mucosa. This study investigated the mechanisms of microRNA (miR)- 340-5p in LC cell proliferation and invasion.
The expression patterns of miR-340-5p, long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1), and matrix metallopeptidase 11 (MMP11) in LC cells, tissues, and para-carcinoma tissues, and human bronchial epithelial cells (HBEC) were examined via RT-qPCR. The effects of elevating or silencing miR-340-5p on LC cell proliferation and invasion were examined. The subcellular localization of lncRNA NEAT1 was determined. The binding relations among miR-340-5p, lncRNA NEAT1, and MMP11 were verified. Functional rescue experiments were designed to verify the functions of lncRNA NEAT1 and MMP11 on LC cell proliferation and invasion. Nude-mouse tumor models were established to assess the role of miR-340-5p in LC in vivo.
miR-340-5p was under-expressed in LC, and miR-340-5p overexpression repressed LC cell proliferation and invasion. Mechanically, miR-340-5p decreased lncRNA NEAT1 stability via directly binding to lncRNA NEAT1 and thus declined lncRNA NEAT1 expression in LC cells, while lncRNA NEAT1 accelerated MMP11 transcription via binding to heat shock factor 1 (HSF1). Overexpression of lncRNA NEAT1 or MMP11 reversed the repression of miR-340-5p overexpression on LC cell proliferation and invasion. In vivo, miR-340-5p overexpression repressed the tumor growth.
miR-340-5p overexpression reduced lncRNA NEAT1 stability via binding to lncRNA NEAT1, which declined lncRNA NEAT1 expression and reduced the binding of lncRNA NEAT1 to HSF1 to further inhibit MMP11 transcription, thus repressing LC cell proliferation and invasion.
喉癌（LC）的诊断相对较少，是一种源自喉黏膜的原发性恶性肿瘤。本研究探讨了微小 RNA（miR）-340-5p 在 LC 细胞增殖和侵袭中的作用机制。
通过 RT-qPCR 检测 LC 细胞、组织和癌旁组织以及人支气管上皮细胞（HBEC）中 miR-340-5p、长链非编码 RNA（lncRNA）核斑组装转录本 1（NEAT1）和基质金属蛋白酶 11（MMP11）的表达模式。通过升高或沉默 miR-340-5p 来检测其对 LC 细胞增殖和侵袭的影响。确定 lncRNA NEAT1 的亚细胞定位。验证 miR-340-5p、lncRNA NEAT1 和 MMP11 之间的结合关系。设计功能恢复实验验证 lncRNA NEAT1 和 MMP11 对 LC 细胞增殖和侵袭的作用。建立裸鼠肿瘤模型评估 miR-340-5p 在 LC 体内的作用。
miR-340-5p 在 LC 中表达下调，过表达 miR-340-5p 抑制 LC 细胞增殖和侵袭。机制上，miR-340-5p 通过直接结合 lncRNA NEAT1 降低 lncRNA NEAT1 的稳定性，从而降低 LC 细胞中的 lncRNA NEAT1 表达，而 lncRNA NEAT1 通过结合热休克因子 1（HSF1）加速 MMP11 转录。过表达 lncRNA NEAT1 或 MMP11 逆转了 miR-340-5p 过表达对 LC 细胞增殖和侵袭的抑制作用。体内，miR-340-5p 过表达抑制肿瘤生长。
miR-340-5p 通过与 lncRNA NEAT1 结合降低其稳定性，从而降低 lncRNA NEAT1 的表达，并减少 lncRNA NEAT1 与 HSF1 的结合，进一步抑制 MMP11 转录，从而抑制 LC 细胞增殖和侵袭。
