PDF(Pubmed)
Abstract：
UNASSIGNED: Recently, emerging studies have validated that circular RNAs participate in multiple biological progresses in various human malignant tumors, including hepatocellular carcinoma (HCC). However, until now, the elucidated mechanism of circular RNAs is only the tip of the iceberg. In this study, we firstly identify a novel circular RNA circRASSF5 (the only circular RNA derived from the RASSF5 gene), and attempt to investigate its biological function and underlying mechanism in HCC.
UNASSIGNED: qRT-PCR, Western blotting and IHC were applied to detect the expression of related genes. CCK-8 assay, EdU staining, wound healing and transwell assays were used to investigate HCC proliferation, migration and invasion abilities. Animal model studies were included to investigate the function of circRASSF5 in HCC tumorigenesis and metastasis. RNA pull-down assay, luciferase reporter assay and FISH (fluorescence in situ hybridization) assay were performed to explore the potential biological mechanism underlying circRASSF5 function in HCC.
UNASSIGNED: CircRASSF5 is obviously downregulated in both HCC tissues and cell lines. Low level of circRASSF5 is negatively associated with larger tumor size, severe vascular invasion, more portal vein tumor embolus and unfavorable prognosis. Loss-of-function assay reveals that circRASSF5 remarkably impedes the growth and metastasis of HCC cells in vitro and in vivo. Mechanistically, circRASSF5 directly interacts with miR-331-3p as a sponge, and then enhances the expression of PH domain and leucine-rich repeat protein phosphatase (PHLPP), thus restraining the progression of HCC cells.
UNASSIGNED: Altogether, we validate that circRASSF5 is a tumor suppressor in HCC, which competitively sponges with miR-331-3p and then enhances the tumor inhibitory effect of PHLPP, indicating the potential application value of circRASSF5 for HCC diagnosis and clinical treatment.
UNASSIGNED: qRT-PCR, Western blotting and IHC were applied to detect the expression of related genes. CCK-8 assay, EdU staining, wound healing and transwell assays were used to investigate HCC proliferation, migration and invasion abilities. Animal model studies were included to investigate the function of circRASSF5 in HCC tumorigenesis and metastasis. RNA pull-down assay, luciferase reporter assay and FISH (fluorescence in situ hybridization) assay were performed to explore the potential biological mechanism underlying circRASSF5 function in HCC.
UNASSIGNED: CircRASSF5 is obviously downregulated in both HCC tissues and cell lines. Low level of circRASSF5 is negatively associated with larger tumor size, severe vascular invasion, more portal vein tumor embolus and unfavorable prognosis. Loss-of-function assay reveals that circRASSF5 remarkably impedes the growth and metastasis of HCC cells in vitro and in vivo. Mechanistically, circRASSF5 directly interacts with miR-331-3p as a sponge, and then enhances the expression of PH domain and leucine-rich repeat protein phosphatase (PHLPP), thus restraining the progression of HCC cells.
UNASSIGNED: Altogether, we validate that circRASSF5 is a tumor suppressor in HCC, which competitively sponges with miR-331-3p and then enhances the tumor inhibitory effect of PHLPP, indicating the potential application value of circRASSF5 for HCC diagnosis and clinical treatment.
摘要：
未经批准：最近，新的研究已经验证了环状RNA参与多种人类恶性肿瘤的生物学进展,包括肝细胞癌（HCC）。然而,直到现在,阐明的环状RNA的机制只是冰山一角。在这项研究中,我们首先鉴定了一个新的环状RNAcircRASSF5（唯一来自RASSF5基因的环状RNA），并试图探讨其在HCC中的生物学功能和潜在机制。
未经鉴定：qRT-PCR，应用Westernblotting和IHC检测相关基因的表达。CCK-8测定，EdU染色,伤口愈合和transwell试验用于研究HCC增殖，迁移和入侵能力。包括动物模型研究circRASSF5在HCC肿瘤发生和转移中的功能。RNA下拉法,进行了荧光素酶报告基因测定和FISH（荧光原位杂交）测定，以探索在HCC中circRASSF5功能潜在的生物学机制。
未经证实：CircRASSF5在肝癌组织和细胞系中明显下调。低水平的circRASSF5与较大的肿瘤大小呈负相关，严重血管侵犯,门静脉癌栓较多，预后不良。功能丧失分析显示，circRASSF5在体外和体内显着阻碍HCC细胞的生长和转移。机械上,circRASSF5作为海绵直接与miR-331-3p相互作用，然后增强PH结构域和富含亮氨酸重复蛋白磷酸酶（PHLPP）的表达，从而抑制HCC细胞的进展。
未经评估：总而言之，我们验证了circRASSF5是肝癌的肿瘤抑制因子，与miR-331-3p竞争海绵，然后增强PHLPP的肿瘤抑制作用，表明circRASSF5在HCC诊断和临床治疗中的潜在应用价值。
未经鉴定：qRT-PCR，应用Westernblotting和IHC检测相关基因的表达。CCK-8测定，EdU染色,伤口愈合和transwell试验用于研究HCC增殖，迁移和入侵能力。包括动物模型研究circRASSF5在HCC肿瘤发生和转移中的功能。RNA下拉法,进行了荧光素酶报告基因测定和FISH（荧光原位杂交）测定，以探索在HCC中circRASSF5功能潜在的生物学机制。
未经证实：CircRASSF5在肝癌组织和细胞系中明显下调。低水平的circRASSF5与较大的肿瘤大小呈负相关，严重血管侵犯,门静脉癌栓较多，预后不良。功能丧失分析显示，circRASSF5在体外和体内显着阻碍HCC细胞的生长和转移。机械上,circRASSF5作为海绵直接与miR-331-3p相互作用，然后增强PH结构域和富含亮氨酸重复蛋白磷酸酶（PHLPP）的表达，从而抑制HCC细胞的进展。
未经评估：总而言之，我们验证了circRASSF5是肝癌的肿瘤抑制因子，与miR-331-3p竞争海绵，然后增强PHLPP的肿瘤抑制作用，表明circRASSF5在HCC诊断和临床治疗中的潜在应用价值。
