Department of Hepatobiliary Surgery, Affiliated Hospital of Jianghan University, Wuhan, China.
Department of Geriatrics, Affiliated Hospital of Jianghan University, Wuhan, China.
Bioengineered. 2022 Jan;13(1):1115-1125. doi: 10.1080/21655979.2021.2017678.
Long non-coding RNAs (lncRNAs) are involved in developing hepatocellular carcinoma (HCC). The present study explored the role of lncRNA LINC01194, which is upregulated in HCC tissues and might be a vital regulator in HCC progression. Levels of LINC01194, microRNA (miR)-655-3p, and SMAD family member 5 (SMAD5) were assessed using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The bioactivity of Huh-7 cells was assessed using cell counting kit-8 and transwell assays and flow cytometry. Western blotting was conducted to measure the expression of invasion- and apoptosis-related proteins. The relationships between lncRNA LINC01194 and miR-655-3p, and miR-655-3p and SMAD5 were predicted using StarBase and TargetScan, and further verified using a dual-luciferase reporter assay. LINC01194 was overexpressed in HCC cells and in clinical samples. ILINC01194 silencing suppressed proliferation and migration; however, it promoted apoptosis in HCC cell lines. We also confirmed that miR-655-3p could bind to LINC01194, and miR-655-3p was downregulated in HCC. The upregulation of miR-655-3p suppressed HCC cell invasion and migration, and enhanced the number of apoptotic cells. SMAD5, which was overexpressed in HCC cell lines, was directly targeted by miR-655-3p. Therefore, LINC01194 promoted HCC development by decreasing miR-655-3p expression and may serve as a promising therapeutic target for HCC patients.
长链非编码 RNA（lncRNA）参与了肝癌（HCC）的发生发展。本研究探讨了在 HCC 组织中上调的 lncRNA LINC01194 的作用，它可能是 HCC 进展的重要调节因子。采用逆转录定量实时聚合酶链反应（RT-qPCR）检测 LINC01194、微小 RNA（miR）-655-3p 和 SMAD 家族成员 5（SMAD5）的水平。采用细胞计数试剂盒-8 和 Transwell 实验及流式细胞术检测 Huh-7 细胞的生物活性。采用 Western blot 检测侵袭和凋亡相关蛋白的表达。采用 StarBase 和 TargetScan 预测 lncRNA LINC01194 与 miR-655-3p、miR-655-3p 与 SMAD5 的关系，并通过双荧光素酶报告基因实验进一步验证。LINC01194 在 HCC 细胞和临床样本中呈过表达。沉默 LINC01194 可抑制 HCC 细胞系的增殖和迁移，但促进其凋亡。我们还证实 miR-655-3p 可与 LINC01194 结合，且在 HCC 中呈低表达。上调 miR-655-3p 可抑制 HCC 细胞侵袭和迁移，增加凋亡细胞数量。SMAD5 在 HCC 细胞系中呈过表达，可直接被 miR-655-3p 靶向。因此，LINC01194 通过降低 miR-655-3p 的表达促进 HCC 的发展，可能成为 HCC 患者有前途的治疗靶点。
