ELFN1-AS1 promotes GDF15-mediated immune escape of colorectal cancer from NK cells by facilitating GCN5 and SND1 association

Abstract

The ability of colorectal cancer (CRC) cells to escape from natural killer (NK) cell immune surveillance leads to anti-tumor treatment failure. The long non-coding RNA (lncRNA) ELFN1-AS1 is aberrantly expressed in multiple tumors suggesting a role as an oncogene in cancer development. However, whether ELFN1-AS1 regulates immune surveillance in CRC is unclear. Here, we determined that ELFN1-AS1 enhanced the ability of CRC cells to escape from NK cell surveillance in vitro and in vivo. In addition, we confirmed that ELFN1-AS1 in CRC cells attenuated the activity of NK cell by down-regulating NKG2D and GZMB via the GDF15/JNK pathway. Furthermore, mechanistic investigations demonstrated that ELFN1-AS1 enhanced the interaction between the GCN5 and SND1 protein and this influenced H3k9ac enrichment at the GDF15 promotor to stimulate GDF15 production in CRC cells. Taken together, our findings indicate that ELFN1-AS1 in CRC cells suppresses NK cell cytotoxicity and ELFN1-AS1 is a potential therapeutic target for CRC.

Role of long non-coding RNA ELFN1-AS1 in carcinogenesis

“…As a result, the suppression of proliferation and migration in vitro was observed. Also, Bin Han et al [ 35 ] showed that ELFN1-AS1 is upregulated in CRC tissues, correlating with poor patient survival. ELFN1-AS1 plays a significant role in CRC by promoting immune escape from natural killer (NK) cell surveillance, by enhancing CRC cells' ability to evade NK cell surveillance both in vitro and in vivo.…”

GDF15: Immunomodulatory Role in Hepatocellular Carcinoma Pathogenesis and Therapeutic Implications

“… 78 GDF15 helps colon cancer cells evade NK cell surveillance by regulating their activity, in which GDF15 expression is regulated by acetylation. 79 In HBV-induced HCC, NK cells have a dual role: they are hepatoprotective and antifibrotic, but their activation can also cause liver damage. 80 NK cell-derived IFN-γ promotes HCC development through the EpCAM-EMT axis in HBV.…”