Long noncoding RNAs (lncRNAs) contribute to the development of hepatocellular carcinoma (HCC), which could regulate various HCC biological characteristics. Here, the study seeks to investigate the role of lncRNA LEF1‐AS1 in HCC cell chemoresistance by regulating microRNA (miR)‐10a‐5p and Musashi1 (MSI1). The microarray‐based analysis was employed to identify the HCC‐related lncRNA‐miRNA‐gene regulatory network. Expression patterns of LEF1‐AS1, miR‐10a‐5p, and MSI1 in the HCC cell lines, tissues were accessed by means of reverse transcription‐quantitative polymerase chain reaction. Next, the interaction among LEF1‐AS1, miR‐10a‐5p, and MSI1 in HCC was accessed by bioinformatics and dual‐luciferase reporter gene assay. Then, the cell line resistant to cisplatin was established, which was then treated with sh/oe‐lncRNA LEF1‐AS1, miR‐10a‐5p‐mimic, and oe/sh‐MSI1 vectors alone or in combination. Afterward, the effect of LEF1‐AS1, miR‐10a‐5p, and MSI1 on HCC cell chemoresistance, proliferation, and apoptosis was assessed. At last, in vivo experiments confirmed the role of MSI1 in tumor growth and chemoresistance in HCC. LEF1‐AS1 might potentially affect the growth and chemoresistance of HCC cells by regulating miR‐10a‐5p and MSI1. LEF1‐AS1 and MSI1 expression patterns were elevated, while miR‐10a‐5p was repressed in HCC tissues and cell lines. LEF1‐AS1 combined to miR‐10a‐5p and regulated MSI1, thereby activating the protein kinase B (AKT) signaling pathway. Knockdown of LEF1‐AS1 and MSI1 or elevation of miR‐10a‐5p compromised the proliferation of Huh7 cell line resistant to DDP and promoted its chemosensitivity and apoptosis. At last, these in vitro findings were also confirmed in vivo. Our results unraveled LEF1‐AS1 acts as a miR‐10a‐5p modulator to promote chemoresistance of HCC cells by stimulating MSI1 and activating the AKT signaling pathway, which might provide a novel therapeutic target for HCC.

中文翻译：

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长非编码RNA LEF1-AS1充当microRNA-10a-5p调节剂，通过激活AKT信号通路增强MSI1表达并促进肝癌细胞的化学耐药性。

长的非编码RNA（lncRNA）有助于肝细胞癌（HCC）的发展，它可以调节各种HCC生物学特性。在此，本研究旨在通过调控microRNA（miR）-10a-5p和Musashi1（MSI1）来研究lncRNA LEF1-AS1在HCC细胞化学抗性中的作用。基于微阵列的分析被用于识别HCC相关的lncRNA-miRNA-基因调控网络。LEF1-AS1，miR-10a-5p和MSI1在HCC细胞系中的表达模式是通过逆转录-定量聚合酶链反应进行的。接下来，通过生物信息学和双萤光素酶报告基因分析来获得肝癌中LEF1-AS1，miR-10a-5p和MSI1之间的相互作用。然后，建立了对顺铂耐药的细胞系，然后用sh / oe-lncRNA LEF1-AS1，miR-10a-5p-mimic，和oe / sh-MSI1载体单独或组合使用。之后，评估了LEF1-AS1，miR-10a-5p和MSI1对HCC细胞化学抗性，增殖和凋亡的影响。最后，体内实验证实了MSI1在HCC的肿瘤生长和化学抗性中的作用。LEF1-AS1可能通过调节miR-10a-5p和MSI1来影响HCC细胞的生长和化学耐药性。LEF1-AS1和MSI1表达模式升高，而miR-10a-5p在HCC组织和细胞系中受到抑制。LEF1-AS1与miR-10a-5p结合并调节MSI1，从而激活蛋白激酶B（AKT）信号通路。敲低LEF1-AS1和MSI1或miR-10a-5p升高会损害对DDP耐药的Huh7细胞系的增殖，并促进其化学敏感性和细胞凋亡。最后，这些体外发现也已在体内得到证实。