Zhu Pengyuan, Huang Haitao, Gu Shaorui, Liu Zhenchuan, Zhang Xin, Wu Kaiqin, Lu Tiancheng, Li Lei, Dong Chenglai, Zhong Chongjun, Zhou Yongxin
Department of thoracic and Cardiovascular Surgery, the Second Affiliated Hospital of Nantong University, School of Medicine, Nantong University, Nantong, 226001, China.
Department of thoracic and Cardiovascular Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
J Cancer. 2021 Jan 1;12(4):1073-1084. doi: 10.7150/jca.51292. eCollection 2021.
Esophageal squamous cell carcinoma (ESCC) is the major subclass of esophageal cancer and one of the most life-threatening malignancies with high morbidity and mortality. Long noncoding RNAs (lncRNAs) participate in tumorigenesis and metastasis of various tumors. Here, we investigated the function of a newly identified lncRNA FAM225A in ESCC. LncRNA FAM225A expression was significantly higher in ESCC and predicted poor prognosis of ESCC patients. We confirmed that upregulation of FAM225A in ESCC and overexpression of FAM225A was associated with poor outcome in ESCC patients using TCGA ESCC cohort. Knockdown of FAM225A significantly inhibited cell growth, migration and invasion of ESCC cells in vitro and inhibited ESCC xenograft development in vivo. Mechanistically, we demonstrated that lncRNA FAM225A functioned as a competing endogenous RNA (ceRNA) via sponging miR-197-5p. LncRNA FAM225A exerted its regulatory function on ESCC proliferation and metastasis via modulating expression of miR-197-5p. MiR-197-5p overexpression antagonized the function of FAM225A, with decreased cell growth and invasion. Moreover, we identified that RNA binding protein NONO was a direct target of miR-197-5p and miR-197-5p negatively regulated NONO expression and TGF-β signaling in ESCC cells. In summary, our findings suggest that lncRNA FAM225A promotes ESCC development and progression via sponging miR-197-5p and upregulating NONO expression. These results suggest that lncRNA FAM225A could be explored as a new therapy target in ESCC treatment.
食管鳞状细胞癌（ESCC）是食管癌的主要亚型，也是发病率和死亡率极高、最具生命威胁的恶性肿瘤之一。长链非编码RNA（lncRNA）参与多种肿瘤的发生和转移。在此，我们研究了新发现的lncRNA FAM225A在ESCC中的功能。lncRNA FAM225A在ESCC中的表达显著升高，并预示着ESCC患者的预后不良。我们利用TCGA ESCC队列证实，ESCC中FAM225A的上调以及FAM225A的过表达与ESCC患者的不良预后相关。敲低FAM225A可显著抑制ESCC细胞在体外的生长、迁移和侵袭，并在体内抑制ESCC异种移植瘤的生长。机制上，我们证明lncRNA FAM225A通过吸附miR-197-5p发挥竞争性内源RNA（ceRNA）的功能。lncRNA FAM225A通过调节miR-197-5p的表达对ESCC的增殖和转移发挥调节作用。miR-197-5p的过表达拮抗了FAM225A的功能，导致细胞生长和侵袭减少。此外，我们确定RNA结合蛋白NONO是miR-197-5p的直接靶点，miR-197-5p在ESCC细胞中负向调节NONO的表达和TGF-β信号通路。总之，我们的研究结果表明，lncRNA FAM225A通过吸附miR-197-5p并上调NONO表达促进ESCC的发生和发展。这些结果表明，lncRNA FAM225A可作为ESCC治疗的新靶点进行探索。
