Liu Chunjiang, Tang Liming, Xu Miaojun, Lin Yuting, Shen Jingfu, Zhou Liang, Ho Lichen, Lu Jinjing, Ai Xiaoming
Department of General Surgery, Shaoxing People's Hospital (Shaoxing Hospital of Zhejiang University) Shaoxing, Zhejiang, China.
Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University Nanjing, Jiangsu, China.
Am J Transl Res. 2021 Mar 15;13(3):1022-1036. eCollection 2021.
Recent studies have proven that there is a relationship between long non-coding RNAs (lncRNAs) and malignant tumor hepatocellular carcinoma (HCC). However, the function of RUSC1-AS1 and its relative regulators in HCC remains unknown.
studies, CCK-8 assays, colony formation assays, transwell assays, and wound healing tests were carried out to evaluate the proliferation, migration, and invasion of HCC cells. The correlation between RUSC1-AS1 expression with tumor size or weight was studied in nude mice. Bioinformatics analysis, dual luciferase, quantitative Real-Time PCR (qRT-PCR), and Western blot analysis aimed to discover the relevance between miR-340-5p and RUSC1-AS1 or cAMP responsive element binding protein 1 (CREB1).
When compared with normal groups, RUSC1-AS1 expression in HCC tissues and HCC cell lines was higher. We also found that knockdown of RUSC1-AS1 inhibited HCC cell progression, including proliferation, migration, and invasion, and suppressed tumorigenesis . Further studies demonstrated that the expression of RUSC1-AS1 negatively correlated with miR-340-5p expression in HCC cells. In addition, miR-340-5p was identified as a direct target of RUSC1-AS1 and tightly associated with the prevention of tumor progression. Moreover, miR-340-5p bound directly to CREB1. CREB1 overexpression reversed the impact of miR-340-5p on HCC cells. Together, lncRNA RUSC1-AS1 plays a regulatory role in the PI3K/AKT signaling pathway in HCC cells.
We demonstrated that lncRNA RUSC1-AS1 influenced HCC cell progression by modulating its downstream target miR-340-5p/CREB1 axis via the PI3K/AKT signaling pathway, which may be a potential prognostic and therapeutic target for treating HCC.
近期研究已证实长链非编码RNA（lncRNAs）与恶性肿瘤肝细胞癌（HCC）之间存在关联。然而，RUSC1-AS1在肝癌中的功能及其相关调控因子仍不清楚。
进行了CCK-8实验、集落形成实验、Transwell实验和伤口愈合实验，以评估肝癌细胞的增殖、迁移和侵袭能力。在裸鼠中研究了RUSC1-AS1表达与肿瘤大小或重量之间的相关性。生物信息学分析、双荧光素酶实验、定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹分析旨在发现miR-340-5p与RUSC1-AS1或环磷酸腺苷反应元件结合蛋白1（CREB1）之间的相关性。
与正常组相比，肝癌组织和肝癌细胞系中RUSC1-AS1的表达更高。我们还发现，敲低RUSC1-AS1可抑制肝癌细胞的进展，包括增殖、迁移和侵袭，并抑制肿瘤发生。进一步研究表明，肝癌细胞中RUSC1-AS1的表达与miR-340-5p的表达呈负相关。此外，miR-340-5p被确定为RUSC1-AS1的直接靶点，并与预防肿瘤进展密切相关。而且，miR-340-5p直接与CREB1结合。CREB1的过表达逆转了miR-340-5p对肝癌细胞的影响。总之，lncRNA RUSC1-AS1在肝癌细胞的PI3K/AKT信号通路中起调节作用
我们证明lncRNA RUSC1-AS1通过PI3K/AKT信号通路调节其下游靶点miR-340-5p/CREB1轴，从而影响肝癌细胞的进展，这可能是治疗肝癌的潜在预后和治疗靶点。
