Drug resistance is one of the major challenges for cancer therapies. In recent years, research on disease-related molecular signaling pathways has become the key ways to understand and overcome obstacles. Dysregulation of MALAT1 could regulate doxorubicin resistance of hepatocellular carcinoma (HCC), but how MALAT1 involving in managing doxorubicin resistance remains unclear yet. We aimed to elucidate the specific molecular mechanism of MALAT1 with doxorubicin resistance in HCC cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was engaged to detect the expression levels of MALAT1, miR-3129-5p and Nova1 mRNA; MTT, western blot, flow cytometry and luciferase reporter assays were executed to identify the influence of MALAT1 on doxorubicin resistance of HCC cells. Xenograft tumor model was created to confirm the biological function of MALAT1 in doxorubicin resistance of HCC cells in vivo. MALAT1 and Nova1 were upregulated, while miR-3129-5p expression was decreased in doxorubicin-resistant HCC tissues and cells. Knockdown of MALAT1 regulated doxorubicin resistance of HCC cells through inhibiting cell proliferation, migration, invasion and promoting apoptosis, but antisense miR-3129-5p released the functional effect of MALAT1 knockdown. Nova1, as a target gene of miR-3129-5p, reversed the results of miR-3129-5p expression and enhanced doxorubicin resistance of HCC cells. Xenograft tumor model suggested that dysregulation of MALAT1 regulated tumor growth and Nova1 to mediate doxorubicin resistance of HCC cells by as a sponge for miR-3129-5p in vivo. Elevation of LncRNA MALAT1 mediated doxorubicin resistance and the progression of HCC via a MALAT1/miR-3129-5p/Nova1 axis. This study would be expected to enrich the understanding of doxorubicin resistance of HCC and provide new ideas for HCC treatment strategies.

中文翻译：

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LncRNA MALAT1通过调节miR-3129-5p/Nova1轴介导肝细胞癌的阿霉素耐药。

耐药性是癌症治疗的主要挑战之一。近年来，对疾病相关分子信号通路的研究已成为认识和克服障碍的关键途径。MALAT1 的失调可以调节肝细胞癌 (HCC) 的阿霉素耐药性，但 MALAT1 如何参与管理阿霉素耐药性尚不清楚。我们旨在阐明 MALAT1 在 HCC 细胞中对阿霉素耐药的具体分子机制。采用定量实时聚合酶链反应（qRT-PCR）检测MALAT1、miR-3129-5p和Nova1 mRNA的表达水平；执行 MTT、蛋白质印迹、流式细胞术和荧光素酶报告基因测定以鉴定 MALAT1 对 HCC 细胞多柔比星抗性的影响。创建异种移植肿瘤模型以确认 MALAT1 在体内 HCC 细胞的多柔比星抗性中的生物学功能。MALAT1 和 Nova1 上调，而 miR-3129-5p 表达在阿霉素耐药的 HCC 组织和细胞中降低。MALAT1 敲低通过抑制细胞增殖、迁移、侵袭和促进细胞凋亡来调节 HCC 细胞的阿霉素耐药，但反义 miR-3129-5p 释放了 MALAT1 敲低的功能作用。Nova1作为miR-3129-5p的靶基因，逆转了miR-3129-5p表达的结果，增强了HCC细胞对阿霉素的耐药性。异种移植肿瘤模型表明，MALAT1 的失调调节了肿瘤生长，Nova1 通过作为 miR-3129-5p 体内 的海绵来介导 HCC 细胞的多柔比星抗性。LncRNA MALAT1 的升高通过 MALAT1/miR-3129-5p/Nova1 轴介导多柔比星耐药性和 HCC 的进展。该研究有望丰富对HCC阿霉素耐药的认识，为HCC治疗策略提供新思路。