Hepatocyte nuclear factor 4 α (HNF4α) is an important transcription factor that acts as a pro-proliferative mediator during tumorigenesis, yet its function in colorectal cancer (CRC) remain unclear. Hence, this study aims to explore roles that HNF4α plays in the CRC development. RNA quantification analysis was conducted to characterize the expression pattern of long intergenic non-coding RNA 00511 (LINC00511)/HNF4α/IL24 in CRC tissues and cell lines. Using gain- and loss-of-function approaches, effects of HNF4α/LINC00511/IL24 axis on biological processes such as proliferative, migrating, invading, apoptotic, and tumorigenic functions of CRC cells were evaluated. We further identified the interactions among HNF4α/LINC00511/EZH2/IL24 using RNA binding protein immunoprecipitation, RNA pull-down along with chromatin immunoprecipitation (ChIP). LINC00511 was an upregulated lncRNA in CRC tissues and cells, which played an oncogenic role by strengthening the malignant phenotypes of CRC cells. LINC00511 down-regulated IL24 expression by interacting with EZH2. HNF4α could enhance LINC00511 transcription in an epigenetic manner, which finally accelerated cancer progression and tumorigenesis through LINC00511-mediated inhibition of IL24. Those data together demonstrated the contribution of HNF4α to the progression of CRC through mediating the LINC00511/EZH2/IL24 axis. Hence, our study provides a promising therapeutic target for CRC.

中文翻译：

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LINC00511依赖性抑制IL24促进HNF4α在大肠癌中的致癌作用

肝细胞核因子4α（HNF4α）是重要的转录因子，在肿瘤发生过程中作为促增殖介质，但其在结直肠癌（CRC）中的功能仍不清楚。因此，本研究旨在探讨HNF4α在CRC发育中的作用。进行RNA定量分析以表征CRC组织和细胞系中长基因间非编码RNA 00511（LINC00511）/HNF4α/ IL24的表达模式。使用功能获得和丧失的方法，评估了HNF4α/ LINC00511 / IL24轴对诸如CRC细胞增殖，迁移，侵袭，凋亡和致瘤功能等生物学过程的影响。我们使用RNA结合蛋白免疫沉淀，RNA下拉以及染色质免疫沉淀（ChIP）进一步鉴定了HNF4α/ LINC00511 / EZH2 / IL24之间的相互作用。LINC00511是CRC组织和细胞中的lncRNA上调，通过增强CRC细胞的恶性表型发挥致癌作用。LINC00511通过与EZH2相互作用下调IL24表达。HNF4α可以以表观遗传的方式增强LINC00511的转录，最终通过LINC00511介导的IL24抑制来加速癌症的进展和肿瘤的发生。这些数据一起证明了HNF4α通过介导LINC00511 / EZH2 / IL24轴对CRC进程的贡献。因此，我们的研究为CRC提供了有希望的治疗靶点。HNF4α可以以表观遗传的方式增强LINC00511的转录，最终通过LINC00511介导的IL24抑制来加速癌症的进展和肿瘤的发生。这些数据一起证明了HNF4α通过介导LINC00511 / EZH2 / IL24轴对CRC进程的贡献。因此，我们的研究为CRC提供了有希望的治疗靶点。HNF4α可以以表观遗传的方式增强LINC00511的转录，最终通过LINC00511介导的IL24抑制来加速癌症的进展和肿瘤的发生。这些数据一起证明了HNF4α通过介导LINC00511 / EZH2 / IL24轴对CRC进程的贡献。因此，我们的研究为CRC提供了有希望的治疗靶点。