LINC00511-dependent inhibition of IL-24 contributes to the oncogenic role of HNF4α in colorectal cancer.

ABSTRACT

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 noncoding RNA 00511 (LINC00511)/HNF4α/IL-24 in CRC tissues and cell lines. Using gain- and loss-of-function approaches, effects of HNF4α/LINC00511/IL-24 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/IL-24 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 downregulated IL-24 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 IL-24. Those data together demonstrated the contribution of HNF4α to the progression of CRC through mediating the LINC00511/EZH2/IL-24 axis. Hence, our study provides a promising therapeutic target for CRC.NEW & NOTEWORTHY Our findings on the roles of hepatocyte nuclear factor 4 α/long intergenic noncoding RNA 00511/IL-24 axis provide new insights into the CRC and offer potential targets for translational applications.