Department of Molecular and Life Science, Hanyang University, Ansan, Republic of Korea.
Institute of Natural Science and Technology, Hanyang University, Ansan, Republic of Korea.
PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poor prognosis. Emerging evidence suggests that epigenetic alterations play a crucial role in HCC, suggesting epigenetic inhibition as a promising therapeutic approach. Indeed, the bromodomain and extra-terminal (BET) inhibitors inhibit the proliferation and invasion of various cancers but still lack a strong mechanistic rationale. Here, we identified the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in human HCC cell line HepG2 treated with the BET inhibitors, JQ1, OTX015, or ABBV-075. We analyzed the correlation between DEmRNAs and DElncRNAs in common for the three inhibitors based on their expression profiles and performed functional annotation pathway enrichment analysis. Most of these shared DEmRNAs and DElncRNAs, including some novel transcripts, were downregulated, indicating decreased proliferation/adhesion and increased apoptosis/inflammation. Our study suggests that BET proteins play a crucial role in regulating cancer progression-related genes and provide a valuable resource for novel putative biomarkers and therapeutic targets in HCC.
肝细胞癌（HCC）是最常见的原发性肝癌，预后不良。新出现的证据表明，表观遗传改变在 HCC 中起着关键作用，这表明表观遗传抑制是一种很有前途的治疗方法。事实上，溴结构域和末端（BET）抑制剂抑制了各种癌症的增殖和侵袭，但仍缺乏强有力的机制基础。在这里，我们鉴定了人肝癌细胞系 HepG2 用 BET 抑制剂 JQ1、OTX015 或 ABBV-075 处理后差异表达的 mRNAs（DEmRNAs）和 lncRNAs（DElncRNAs）。我们根据它们的表达谱分析了三种抑制剂共有的 DEmRNAs 和 DElncRNAs 之间的相关性，并进行了功能注释途径富集分析。这些共同的 DEmRNAs 和 DElncRNAs 中的大多数，包括一些新的转录物，都被下调，表明增殖/黏附减少，凋亡/炎症增加。我们的研究表明，BET 蛋白在调节与癌症进展相关的基因中起着至关重要的作用，并为 HCC 中的新型潜在生物标志物和治疗靶点提供了有价值的资源。
