Li Hao Miao, Yu Yong Kui, Liu Qi, Wei Xiu Feng, Zhang Jun, Zhang Rui Xiang, Sun Hai Bo, Wang Zong Fei, Xing Wen Qun, Li Yin
Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Department of Thoracic Surgery, The Cancer Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Onco Targets Ther. 2020 Jan 24;13:757-767. doi: 10.2147/OTT.S224550. eCollection 2020.
Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) has been reported to be aberrantly expressed and plays an important role in human cancers, including esophageal squamous cell cancer. However, the regulatory mechanism underlying SNHG1 in the progression of esophageal squamous cell cancer is poorly defined.
Fifty-three esophageal squamous cell cancer patients were recruited and overall survival was analyzed. EC9706 and KYSE150 cells were cultured for study in vitro. The expression levels of SNHG1, microRNA (miR)-204 and homeobox c8 (HOXC8) were detected by quantitative real-time polymerase chain reaction and Western blot. Cell cycle distribution, apoptosis, migration and invasion were determined by flow cytometry and transwell assays, respectively. The target interaction among SNHG1, miR-204 and HOXC8 was validated by luciferase reporter assay and RNA immunoprecipitation. Xenograft model was established to investigate the role of SNHG1 in vivo.
High expression of SNHG1 was exhibited in esophageal squamous cell cancer and indicated poor outcomes of patients. SNHG1 silence led to cell cycle arrest at G0-G1 phase, inhibition of migration and invasion and increase of apoptosis. miR-204 was validated to sponge by SNHG1 and target HOXC8 in esophageal squamous cell cancer cells. miR-204 knockdown or HOXC8 restoration reversed the inhibitive role of SNHG1 silence in the progression of esophageal squamous cell cancer cells. Furthermore, inhibiting SNHG1 decreased xenograft tumor growth by regulating miR-204 and HOXC8.
SNHG1 knockdown suppresses migration and invasion but induces apoptosis of esophageal squamous cell cancer cells by increasing miR-204 and decreasing HOXC8.
长链非编码RNA小核仁RNA宿主基因1（SNHG1）已被报道在包括食管鳞状细胞癌在内的人类癌症中异常表达并发挥重要作用。然而，SNHG1在食管鳞状细胞癌进展中的调控机制尚不清楚。
招募53例食管鳞状细胞癌患者并分析其总生存期。培养EC9706和KYSE150细胞用于体外研究。通过定量实时聚合酶链反应和蛋白质免疫印迹法检测SNHG1、微小RNA（miR）-204和同源盒c8（HOXC8）的表达水平。分别通过流式细胞术和Transwell实验确定细胞周期分布、细胞凋亡、迁移和侵袭情况。通过荧光素酶报告基因实验和RNA免疫沉淀验证SNHG1、miR-204和HOXC8之间的靶向相互作用。建立异种移植模型以研究SNHG1在体内的作用。
食管鳞状细胞癌中呈现SNHG1高表达，提示患者预后不良。SNHG1沉默导致细胞周期停滞于G0-G1期，抑制迁移和侵袭，并增加细胞凋亡。在食管鳞状细胞癌细胞中，miR-204被证实为SNHG1的海绵吸附分子并靶向HOXC8。miR-204敲低或HOXC8恢复可逆转SNHG1沉默对食管鳞状细胞癌细胞进展的抑制作用。此外，抑制SNHG1可通过调节miR-204和HOXC8减少异种移植瘤的生长。
SNHG1敲低通过增加miR-204和降低HOXC8抑制食管鳞状细胞癌细胞的迁移和侵袭，但诱导其凋亡。
