Zhao Liang, Zang Qing, Liang Guodong, Yao Xiaobin
Department of General Surgery, Gansu Gem Flower Hospital, Lanzhou 730060, Gansu, China.
Department of Emergency, Gansu Gem Flower Hospital, Lanzhou 730060, Gansu, China.
Heliyon. 2023 Sep 7;9(9):e19862. doi: 10.1016/j.heliyon.2023.e19862. eCollection 2023 Sep.
As an important factor tumor regulator，long non-coding RNAs (lncRNAs) have aroused extensive attention via the diverse functional mechanisms that were associated with the pathological and physiological processes of HCC. Here, the main purpose of this study was to provide a clear understanding about the expression, functions and potential mechanism of lncRNA CECR7 (Cat Eye Syndrome Chromosome Region, Candidate 7) in HCC.
RT-qPCR analysis and TCGA database analysis were applied to investigate the expression of CECR7 in HCC cell lines and tissues. Chi-squared Test was employed to explore the correlation between CECR7 expression and HCC clinicopathological features. Besides, Kaplan-Meier curves were constructed to test the effects of CECR7 expression on the prognosis of HCC patients. Transwell assays, MTT assay EdU assay and animal experiments were applied to explore the effects of CECR7 expression on HCC cells migration, invasion, and growth. Furthermore, RNA-seq analysis, luciferase reporter assay and mRNA decay rates assessment were utilized to investigate the mechanism whereby CECR7 regulated EXO1 mRNA. And, rescue experiments were used to determine whether EXO1 was an essential mediator for CECR7 to accelerate HCC cells migration, invasion, and growth.
CECR7 was determined to be significantly overexpressed in HCC cell lines and tissues. CECR7 expression was closely correlated with the tumor size, venous infiltration, TNM stage, 5-year overall survival and disease-free survival of HCC. And, CECR7 played a catalytic role in HCC cells migration, invasion, and growth. Furthermore, CECR7 enhanced the stability of EXO1 mRNA by recruiting RNA binding protein U2AF2. And, EXO1 was determined to be an essential mediator for CECR7 to accelerate HCC cells migration, invasion, and growth.
In a word, our findings demonstrates that the cancer-promoting gene lncRNA CECR7 motivates HCC metastasis and growth through enhanced mRNA stability of EXO1 mediated by U2AF2, proposing a new insight for targeted therapy of HCC.
作为肿瘤调节的一个重要因素，长链非编码RNA（lncRNAs）通过与肝癌（HCC）病理生理过程相关的多种功能机制引起了广泛关注。本研究的主要目的是明确lncRNA CECR7（猫眼综合征染色体区域候选基因7）在肝癌中的表达、功能及潜在机制。
应用RT-qPCR分析和TCGA数据库分析来研究CECR7在肝癌细胞系和组织中的表达。采用卡方检验探讨CECR7表达与肝癌临床病理特征之间的相关性。此外，构建Kaplan-Meier曲线以检测CECR7表达对肝癌患者预后的影响。运用Transwell实验、MTT实验、EdU实验及动物实验来探究CECR7表达对肝癌细胞迁移、侵袭和生长的影响。此外，利用RNA测序分析、荧光素酶报告基因检测和mRNA降解率评估来研究CECR7调控EXO1 mRNA的机制。并且，通过拯救实验来确定EXO1是否是CECR7促进肝癌细胞迁移、侵袭和生长的关键介质。
确定CECR7在肝癌细胞系和组织中显著过表达。CECR7表达与肝癌的肿瘤大小、静脉浸润、TNM分期、5年总生存率和无病生存率密切相关。并且，CECR7在肝癌细胞迁移、侵袭和生长中起促进作用。此外，CECR7通过招募RNA结合蛋白U2AF2增强EXO1 mRNA的稳定性。并且，确定EXO1是CECR7促进肝癌细胞迁移、侵袭和生长的关键介质。
总之，我们的研究结果表明，促癌基因lncRNA CECR7通过U2AF2介导的EXO1 mRNA稳定性增强促进肝癌转移和生长，为肝癌的靶向治疗提供了新的见解。
