Zhen-Hua Wu, Yi-Wei Gong, Li-Qin Zhao, Jie-Yun Zhang, Zhe Gong, Wei-Jian Guo
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Oncol. 2020 Sep 2;10:1508. doi: 10.3389/fonc.2020.01508. eCollection 2020.
Numerous studies have shown that lncRNAs play vital roles in the development and progression of cancer. However, investigations of lncRNAs in gastric cancer are limited and need to be further pursued. According to RNA-seq results of gastric cancer (GC) tissues, we identified a novel lncRNA, C1RL-AS1. qRT-PCR was used to detect the expression level of C1RL-AS1 in paired GC and normal tissues. Nuclear/cytoplasmic fractionation was applied to evaluate the distribution of C1RL-AS1 in GC cells. For functional evaluation, CCK-8, colony formation, transwell, and apoptosis assays were used to determine the oncogenic role of C1RL-AS1. C1RL-AS1 was upregulated in GC tissues, and high expression levels of C1RL-AS1 were associated with poor prognosis. Further functional assays revealed that silencing C1RL-AS1 attenuated the proliferation rate and migration ability and enhanced the apoptotic rate and the senescence of GC cells. The subsequent underlying mechanistic investigation revealed that Wnt/β-catenin was involved in C1RL-AS1-mediated signaling. Rescue experiments suggested that C1RL-AS1 probably promoted the malignant phenotype via the AKT/β-catenin pathway by downregulating c-Myc. C1RL-AS1 probably exerts its biological function by mediating the AKT/β-catenin/c-Myc pathway, indicating a novel therapeutic target in GC.
众多研究表明，长链非编码RNA（lncRNAs）在癌症的发生发展过程中发挥着至关重要的作用。然而，针对胃癌中lncRNAs的研究较为有限，仍需进一步深入探究。根据胃癌（GC）组织的RNA测序结果，我们鉴定出一种新型lncRNA，即C1RL-AS1。采用qRT-PCR检测配对的GC组织和正常组织中C1RL-AS1的表达水平。运用细胞核/细胞质分级分离法评估C1RL-AS1在GC细胞中的分布情况。为进行功能评估，采用CCK-8、集落形成、Transwell和凋亡检测等方法来确定C1RL-AS1的致癌作用。C1RL-AS1在GC组织中上调，其高表达水平与预后不良相关。进一步的功能检测表明，沉默C1RL-AS1可降低GC细胞的增殖率和迁移能力，并提高其凋亡率和衰老程度。随后的潜在机制研究显示，Wnt/β-连环蛋白参与了C1RL-AS1介导的信号传导。挽救实验表明，C1RL-AS1可能通过下调c-Myc，经由AKT/β-连环蛋白途径促进恶性表型的形成。C1RL-AS1可能通过介导AKT/β-连环蛋白/c-Myc途径发挥其生物学功能，这表明其是GC中的一个新型治疗靶点。
