hsa_circ_0072309 Inhibits Oncogenesis in Hepatocellular Carcinoma by Epigenetic Activation of its Host Gene

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Biochemistry and Biophysics Pub Date : 2024-09-16 DOI:10.1007/s12013-024-01330-9
Tao Wang, Yanan Du, Haiyang Song, Jiewei Sun, Wenjin Jiang, Zhiying Xu
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Abstract

Recently, numerous studies have revealed the participation of circular RNAs (circRNAs) in cancer progression. Likewise, this research focused on circRNAs in hepatocellular carcinoma (HCC). A lowly expressed circRNA hsa_circ_0072309 in HCC was screened by analyzing the circRNA microarray GSE242797 and GSE216115 and identified in clinical specimens and cells. Subsequently, CCK-8, colony formation, and transwell assays were performed. The results revealed that hsa_circ_0072309 overexpression suppressed HCC cell proliferation, migration, invasion, and sorafenib resistance, whereas its suppression showed opposite results. Mechanistic investigation found an interaction between hsa_circ_0072309 and its host gene leukemia inhibitory factor receptor (LIFR) in HCC. We found that LIFR overexpression promoted the hsa_circ_0072309 formation. In turn, hsa_circ_0072309 recruited the E1A binding protein p300 to promote the enrichment of H3K27 acetylation (H3K27ac) in the LIFR enhancer, thus transcriptionally promoting LIFR expression. To conclude, we revealed a hsa_circ_0072309/LIFR regulatory loop in HCC, which may provide a potential target for HCC treatment.

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hsa_circ_0072309 通过表观遗传激活宿主基因抑制肝细胞癌的肿瘤发生
最近,许多研究揭示了环状 RNA(circRNA)在癌症进展中的参与作用。同样,本研究也关注肝细胞癌(HCC)中的环状 RNA。通过分析 circRNA 微阵列 GSE242797 和 GSE216115,筛选出了一种在 HCC 中低表达的 circRNA hsa_circ_0072309,并在临床标本和细胞中进行了鉴定。随后,进行了 CCK-8、集落形成和转孔试验。结果发现,过表达 hsa_circ_0072309 会抑制 HCC 细胞的增殖、迁移、侵袭和索拉非尼抗性,而抑制 hsa_circ_0072309 则会产生相反的结果。机理研究发现,hsa_circ_0072309与其宿主基因白血病抑制因子受体(LIFR)在HCC中存在相互作用。我们发现 LIFR 的过表达促进了 hsa_circ_0072309 的形成。反过来,hsa_circ_0072309 招募 E1A 结合蛋白 p300,促进 LIFR 增强子中 H3K27 乙酰化(H3K27ac)的富集,从而转录促进 LIFR 的表达。总之,我们揭示了HCC中的hsa_circ_0072309/LIFR调控环,这可能为HCC的治疗提供一个潜在的靶点。
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来源期刊
Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
72
审稿时长
7.5 months
期刊介绍: Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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