LINC00657 knockdown suppresses hepatocellular carcinoma progression by sponging miR-424 to regulate PD-L1 expression
LINC00657 knockdown suppresses hepatocellular carcinoma progression by sponging miR-424 to regulate PD-L1 expression
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DOI：
10.1007/s13258-020-01001-y
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发表时间：
2020-09-29
期刊：
影响因子：
2.1
通讯作者：
Tursun, Turgunjan
中科院分区：
文献类型：
--
作者：
Cao, Xinling;Zhang, Guanping;Tursun, Turgunjan
背景肝细胞癌（HCC）是世界范围内第六大最常见的恶性肿瘤，也是第四大癌症相关死亡原因。LINC 00657作为一种新的非编码RNA，首次被鉴定为在乳腺癌中具有致癌作用。然而，很少有研究关注LINC 00657对HCC进展的影响。目的研究LINC 00657对肝癌组织和细胞的作用，并探讨其作用机制。方法采用qRT-PCR方法检测LINC 00657在肝癌组织和细胞系中的表达。接下来，我们在HCC细胞中建立了LINC 00657敲低。采用CCK-8实验、细胞侵袭实验、流式细胞术分析、qRT-PCR和western blotting等方法研究LINC 00657基因敲低对肝癌细胞生物学行为的影响。通过生物信息学分析和拯救实验对该蛋白的作用机制进行了研究。结果LINC 00657在肝癌组织和细胞系中过表达，预后差。LINC 00657基因敲低抑制肝癌细胞的增殖和侵袭，促进细胞凋亡。生物信息学分析显示LINC 00657吸收miR-424作为ceRNA。此外，PD-L1模拟物挽救了si-LINC 00657对HCC细胞生物学行为的抑制。结论LINC 00657可能通过吞噬miR-424调控PD-L1的表达，从而影响肝癌的发生发展。这些结果可能为LINC 00657在肝细胞癌中的治疗应用提供新的证据。
Background Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed malignant tumor and the fourth leading cause of cancer-related deaths worldwide. As a novel non-coding RNA, LINC00657 was firstly identified as an oncogenic role in breast cancer. However, few research focus on the effect of LINC00657 on the progression of HCC. Objectives The purpose of this study was to investigate the effect of LINC00657 on HCC tissues and cells, and further explore the potential mechanism. Methods We first measured the expression of LINC00657 in HCC tissues and cell lines using qRT-PCR. Next we established LINC00657 knockdown in HCC cells. CCK-8 assay, cell invasion assay, flow cytometry analysis, qRT-PCR and western blotting were applied to assess the role of LINC00657 knockdown in the biological behavior of HCC cells. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism. Results LINC00657 was remarkably overexpressed in HCC tissues and cell lines, associated with poor prognosis. LINC00657 knockdown repressed cell proliferation and invasion, promoted cell apoptosis of HCC cell lines. The bioinformatics analysis showed LINC00657 sponged miR-424 as a ceRNA. Besides, PD-L1 mimic rescued the suppression of si-LINC00657 in the biological behavior of HCC cells. Conclusion In a word, we observed LINC00657 regulated PD-L1 expression by sponging miR-424, thus affecting the developments of hepatocellular carcinoma. These findings LINC00657 may provide new evidence for therapeutic application in hepatocellular carcinoma.