LncRNA CRNDE is involved in radiation resistance in hepatocellular carcinoma via modulating the SP1/PDK1 axis
LncRNA CRNDE is involved in radiation resistance in hepatocellular carcinoma via modulating the SP1/PDK1 axis
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DOI：
10.4149/neo_2022_211230n1853
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发表时间：
2022-01-01
期刊：
影响因子：
3
通讯作者：
Duan, Xiao-Peng
中科院分区：
文献类型：
--
作者：
Chen, Kai-Yun;Zhu, Shu-Guang;Duan, Xiao-Peng
肝细胞癌（Hepatocellular carcinoma，HCC）是一种常见的恶性肿瘤，放射治疗是其有效的治疗手段，本研究旨在探讨长链非编码RNA（long non-coding RNA，lncRNA）大肠癌差异表达基因（colorectal neoplasia differentially expressed gene，CRNDE）在HCC放射抵抗中的作用机制。在HCC细胞中检测到LncRNA CRNDE上调。建立了抗辐射细胞株Huh 7 R和SNU-387 R。在沉默lncRNA CRNDE后，细胞集落形成能力、细胞活性、凋亡、细胞周期和细胞增殖能力均降低。H2 AX在Huh 7 R和SNU-387 R中的阳性率分别为100%和100%。沉默lncRNA CRNDE降低细胞活性、集落形成能力和G2期细胞数量，并促进DNA损伤和凋亡。证实了特异性蛋白1（SP1）与lncRNACRNDE和3-磷酸肌醇依赖性蛋白激酶1（PDK 1）的结合关系。LncRNA CRNDE通过与转录因子SP1结合来调节PDK 1的转录。PDK 1过表达部分逆转了沉默lncRNA CRNDE对肝癌细胞辐射抗性的抑制作用。建立了移植性肿瘤小鼠模型，并显示沉默lncRNA CRNDE在体内降低了HCC小鼠中的肿瘤体积和重量以及Ki 67阳性细胞。总的来说，lncRNA CRNDE在HCC细胞中上调，并通过与SP1结合促进PDK 1转录，从而增强HCC细胞的辐射抗性。
Hepatocellular carcinoma (HCC) is defined as a universal malignancy while radiation therapy is the effective treatment for it. This study validated the mechanism of long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed gene (CRNDE) in radiation resistance in HCC. LncRNA CRNDE upregulation was detected in HCC cells. The radiation-resistant cell strains Huh7R and SNU-387R were established. After silencing lncRNA CRNDE, the cell colony formation ability, cell activity, apoptosis, cell cycles, and.-H2AX positive rate in Huh7R and SNU-387R were detected. Silencing lncRNA CRNDE decreased the cell activity, colony formation ability, and cell number in the G2 phase and facilitated DNA damage and apoptosis. The binding relations of specificity protein 1 (SP1) with lncRNA CRNDE and 3-phosphoinositide dependent protein kinase 1 (PDK1) were verified. LncRNA CRNDE regulated PDK1 transcription by binding to transcription factor SP1. PDK1 overexpression partially reversed the inhibition of silencing lncRNA CRNDE on radiation resistance in HCC cells. The transplanted tumor mouse model was established and showed that silencing lncRNA CRNDE decreased tumor volume and weight and Ki67-positive cells in HCC mice in vivo. Collectively, lncRNA CRNDE was upregulated in HCC cells and promoted PDK1 transcription by binding to SP1, thus enhancing radiation resistance in HCC cells.