Department of General Surgery, Xi'an Children's Hospital, Xi'an, China.
Eur Rev Med Pharmacol Sci. 2021 Oct;25(20):6208-6219. doi: 10.26355/eurrev_202110_26991.
LINC00205, a bidirectional lncRNA, located at human chromosome 21q22.3, was recently characterized as an oncogenic molecule contributing to cell proliferation in several cancers, including hepatocellular carcinoma (HCC). In the present study, we aim to probe the new molecular mechanism for LINC00205 controlling the proliferation of HCC cells.
The expression status of LINC00205, miR-26a-5p, as well as CDK6 in HCC tissues/cell lines was determined by quantitative real-time PCR (qPCR). The cell proliferative activity was measured by using the Cell Counting Kit (CCK)-8 assay. Flow cytometry was performed to analyze cell cycle progression and apoptosis induction. The interaction among LINC00205, miR-26a-5p and CDK6, as well as transcription efficiency of LINC00205 promoter were examined by Dual-Luciferase reporter assay. Western blot was conducted to evaluate the protein levels of CDK6 in SNU-449 cells. The direct interplay between YY1 and LINC00205 promoter was detected by ChIP-qPCR.
LINC00205 was strongly expressed in HCC tissues and cell lines. Elevated LINC00205 expression was positively associated with worse prognosis as well as pathological grade in HCC. Suppression of LINC00205 could impede the proliferation of HCC cells by triggering the G0/G1-phase cell cycle arrest and apoptosis in vitro. Mechanistically, we illustrated that LINC00205 could accelerate the proliferation of HCC cells by boosting CDK6 expression via sponging miR-26a-5p. Moreover, we unveiled that LINC00205 could be activated by transcription factor Yin Yang-1 (YY1) as its direct downstream target.
LINC00205, a novel YY1-modulated lncRNA, can facilitate the proliferation of HCC cells through YY1/miR-26a-5p/CDK6 pathway, and may serve as a promising diagnostic biomarker and therapeutic target for HCC.
LINC00205 是一种双向长非编码 RNA，位于人类染色体 21q22.3，最近被描述为一种致癌分子，可促进包括肝细胞癌（HCC）在内的几种癌症中的细胞增殖。在本研究中，我们旨在探究控制 HCC 细胞增殖的 LINC00205 的新分子机制。
通过实时定量 PCR（qPCR）测定 HCC 组织/细胞系中 LINC00205、miR-26a-5p 和 CDK6 的表达状态。使用细胞计数试剂盒（CCK-8）测定细胞增殖活性。通过流式细胞术分析细胞周期进程和凋亡诱导。通过双荧光素酶报告基因检测分析 LINC00205、miR-26a-5p 和 CDK6 之间的相互作用以及 LINC00205 启动子的转录效率。Western blot 检测 SNU-449 细胞中 CDK6 的蛋白水平。通过 ChIP-qPCR 检测 YY1 和 LINC00205 启动子之间的直接相互作用。
LINC00205 在 HCC 组织和细胞系中表达强烈。LINC00205 表达升高与 HCC 患者的预后不良以及病理分级呈正相关。体外抑制 LINC00205 可通过触发 G0/G1 期细胞周期阻滞和凋亡来抑制 HCC 细胞的增殖。机制上，我们表明 LINC00205 通过海绵 miR-26a-5p 来加速 CDK6 的表达从而促进 HCC 细胞的增殖。此外，我们揭示 LINC00205 可以作为其直接下游靶标被转录因子 Yin Yang-1 (YY1) 激活。
LINC00205 是一种新的 YY1 调节的长非编码 RNA，可通过 YY1/miR-26a-5p/CDK6 通路促进 HCC 细胞的增殖，可能成为 HCC 的一种有前途的诊断生物标志物和治疗靶点。
