Department of Stomatology, Jinling Hospital, Jinling Clinical College of Nanjing Medical University, Nanjing, China.
Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
Oral Dis. 2022 Oct;28(7):1871-1881. doi: 10.1111/odi.13841. Epub 2021 Apr 28.
This study sought to investigate the effect of miR-5191 on proliferation, invasion and metastasis in salivary adenoid cystic carcinoma (SACC).
The differential expression level of miR-5191 between 5 primary tumor and adjacent non-neoplastic samples, and in two SACC cell lines was detected by quantitative real-time PCR. Cell proliferation, invasion, and migration were performed, followed by luciferase reporter assay and western analysis. The effect of miR-5191 on cell proliferation and apoptosis was evaluated by cell growth and apoptosis assay. The function of miR-5191 in SACC tumorigenesis and metastasis in vivo was investigated by nude mice experiment. The associations between miR-5191/Notch-2 expression and clinicopathological features were analyzed.
miR-5191 was downregulated in primary tumor tissues and SACC-LM cells. By targeting Notch-2, miR-5191 expression level affected the migration, invasion, and proliferation of SACC cells. Overexpression of miR-5191 inhibited the expression levels of Notch-2, followed by the decreased expression of c-Myc, Bcl-2, Hes-1, Hey-1, and Cyclin D1. In vivo, miR-5191 overexpression suppressed the SACC tumorigenesis and pulmonary metastasis in mice. In SACC patients, higher expression of miR-5191 was related to better prognoses and lower possibility of metastasis.
miR-5191 acts as a tumor suppressor in SACC by targeting Notch-2.
本研究旨在探讨 miR-5191 对唾液腺腺样囊性癌（SACC）增殖、侵袭和转移的影响。
通过实时定量 PCR 检测 miR-5191 在 5 例原发肿瘤和相邻非肿瘤样本及两种 SACC 细胞系中的差异表达水平。进行细胞增殖、侵袭和迁移实验，随后进行荧光素酶报告基因检测和 Western 分析。通过细胞生长和凋亡实验评估 miR-5191 对细胞增殖和凋亡的影响。通过裸鼠实验研究 miR-5191 对 SACC 肿瘤发生和转移的体内作用。分析 miR-5191/Notch-2 表达与临床病理特征的关系。
miR-5191 在原发肿瘤组织和 SACC-LM 细胞中下调。通过靶向 Notch-2，miR-5191 的表达水平影响 SACC 细胞的迁移、侵袭和增殖。过表达 miR-5191 抑制 Notch-2 的表达水平，随后下调 c-Myc、Bcl-2、Hes-1、Hey-1 和 Cyclin D1 的表达。在体内，miR-5191 的过表达抑制了小鼠的 SACC 肿瘤发生和肺转移。在 SACC 患者中，miR-5191 的高表达与更好的预后和更低的转移可能性相关。
miR-5191 通过靶向 Notch-2 发挥 SACC 的肿瘤抑制作用。
