Background: 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.
Methods: In vitro 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).
Results: 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 in vivo. 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.
Conclusion: 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.
Keywords: CREB1; LncRNA RUSC1-AS1; hepatocellular carcinoma; invasion; miR-340-5p.
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