Abstract
Unveiling key oncogenic events in malignancies is the key to improving the prognosis and therapeutic outcome of malignancies. Lines of evidence have shown that super-enhancers control the expression of genes that determine the cell fate, but the oncogenic super-enhancers in colorectal cancer (CRC) and their impact on carcinogens remain largely unexplored. Here, we identified a new oncogenic super-enhancer-regulated gene, IL-20RA, in CRC. Using the integrative analysis of H3K27ac ChIP-seq and RNA-seq in CRC tumors and normal colon tissues, we obtained a series of oncogenic super-enhancers in CRC. We found that super-enhancer inhibition by JQ-1 or iBET-151 suppressed the growth of tumor cells and inhibited the expression of IL-20RA. We found that IL-20RA was highly expressed in the tumor tissue of CRC and related to the advanced stage. Further functional studies showed that knockdown of IL-20RA inhibited the growth and metastasis of CRC. In addition, we found that IL-20RA was involved in regulating oncogenic and immune pathways and affecting the expression of genes related to cell proliferation and immune evasion in CRC. Together, our study demonstrated a novel oncogene in CRC and shed new light on oncogenic super-enhancer contributions to cell proliferation and immune escape.
Highlights
Colorectal cancer (CRC) was the third most commonly diagnosed cancer and the second leading cause of cancer death in global cancer statistics in 2020 [1]
These super-enhancers were assigned to nearby genes, and gene ontology analysis showed that these super-enhancer-regulated genes related to transcription regulation, apoptosis and cell death were identified (Figure 1B), which is in accordance with previous studies [6]
Our study demonstrates that SEs are highly expressed in colorectal cancer, which suggests that SEs are related to the occurrence and development of CRC
Summary
Colorectal cancer (CRC) was the third most commonly diagnosed cancer and the second leading cause of cancer death in global cancer statistics in 2020 [1]. In China, the mortality of CRC increased from 6 (1990) to 13 (2017) per 100,000 individuals [2]. Radical resection is recognized as the main treatment for CRC. Most CRC patients are diagnosed at an advanced stage or with metastasis, and require chemotherapy, immunotherapy, or targeted therapy. Finding novel targets at the molecular level is critical to improve the early diagnosis, treatment and prognosis of CRC
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