Am J Physiol Gastrointest Liver Physiol. 2020 Oct 14. doi: 10.1152/ajpgi.00243.2020. Online ahead of print.
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.