The Second School of Clinical Medicine, Southern Medical University Guangzhou, Guangdong, Baiyun, China.
Department of Otorhinolaryngology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, China.
Technol Cancer Res Treat. 2021 Jan-Dec;20:1533033821990074. doi: 10.1177/1533033821990074.
Laryngeal cancer is one of the most common malignant tumors among head and neck cancers. Accumulating studies have indicated that long noncoding RNAs (lncRNAs) play an important role in laryngeal cancer occurrence and progression, however, the functional roles and relative regulatory mechanisms of lncRNA growth arrest-specific transcript 5 (GAS5) in laryngeal cancer progression remain unclear.
The expression of lncRNA GAS5 in both laryngeal cancer tissues and cell lines was evaluated using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. The relationships between lncRNA GAS5 expression and clinical parameters were also analyzed. To determine the biological function of lncRNA GAS5, a lncRNA GAS5-specific plasmid was first transfected into laryngeal cancer cells using lentiviral technology. Cell counting kit-8 assay, flow cytometry, and Transwell assays were used to detect cell proliferation, apoptosis, cycle distribution, and metastasis abilities, respectively. Furthermore, in vivo cell growth experiments were also performed using nude mice. Additionally, western blotting was performed to identify the underlying regulatory mechanism.
In the current study, lncRNA GAS5 was downregulated in laryngeal cancer tissues and its low expression was closely associated with poor tumor differentiation, advanced TNM stage, lymph node metastasis, and shorter overall survival time. In addition, lncRNA GAS5 upregulation significantly inhibited laryngeal cancer cell proliferation both and . Moreover, in response to lncRNA GAS5 overexpression, more laryngeal cancer cells were arrested at the G2/M stage, accompanied by increased cell apoptosis rates and suppressed migration and invasion capacities. Mechanistically, our data showed that the overexpression of lncRNA GAS5 significantly regulated the PI3K/AKT/mTOR signaling pathway.
LncRNA GAS5 might act as a suppressor gene during laryngeal cancer development, as it suppressed cell proliferation and metastasis by regulating the PI3K/AKT/mTOR signaling pathway; thus, lncRNA GAS5 is a promising therapeutic biomarker for the treatment of laryngeal cancer.
喉癌是头颈部癌症中最常见的恶性肿瘤之一。越来越多的研究表明，长非编码 RNA（lncRNA）在喉癌的发生和发展中起着重要作用，然而，lncRNA 生长停滞特异性转录物 5（GAS5）在喉癌进展中的功能作用和相对调节机制尚不清楚。
采用实时定量逆转录聚合酶链反应（RT-qPCR）检测喉癌组织和细胞系中 lncRNA GAS5 的表达，并分析 lncRNA GAS5 表达与临床参数的关系。为了确定 lncRNA GAS5 的生物学功能，首先采用慢病毒技术将 lncRNA GAS5 特异性质粒转染入喉癌细胞。采用细胞计数试剂盒-8 法、流式细胞术和 Transwell 实验分别检测细胞增殖、凋亡、细胞周期分布和转移能力。此外，还采用裸鼠进行体内细胞生长实验。此外，还进行了 Western blot 实验以确定潜在的调节机制。
在本研究中，lncRNA GAS5 在喉癌组织中下调，其低表达与肿瘤分化不良、TNM 分期较晚、淋巴结转移和总生存时间较短密切相关。此外，lncRNA GAS5 的上调显著抑制了喉癌细胞的增殖。此外，lncRNA GAS5 过表达时，更多的喉癌细胞停滞在 G2/M 期，同时细胞凋亡率增加，迁移和侵袭能力受到抑制。机制研究表明，lncRNA GAS5 的过表达显著调节了 PI3K/AKT/mTOR 信号通路。
lncRNA GAS5 可能在喉癌发生过程中作为一种抑制基因发挥作用，通过调节 PI3K/AKT/mTOR 信号通路抑制细胞增殖和转移；因此，lncRNA GAS5 是治疗喉癌的有前途的治疗生物标志物。
