TY  - JOUR
T1  - CircPHLPP2 Facilitates Colorectal Cancer Progression and Anti-PD-1 Resistance via ILF3-Mediated Regulation of IL36γ Transcription
A1  - Alexei Sergeyevich Volkov
A1  - Dmitry Igor Kuzmin
JF  - Archive of International Journal of Cancer and Allied Science
JO  - Arch Int J Cancer Allied Sci
SN  - 3108-4834
Y1  - 2023
VL  - 3
IS  - 2
DO  - 10.51847/HMsHY9e0OQ
SP  - 48
EP  - 68
N2  - Most patients with colorectal cancer (CRC) show a poor response to anti-programmed cell death protein 1 (PD-1) therapy, and the mechanisms behind this resistance are not well understood. Circular RNAs (circRNAs) have been recognized as key regulators in tumor development and progression, with potential utility in cancer detection and predicting therapeutic outcomes. Despite this, the involvement of circRNAs in immune evasion in CRC remains largely unexplored.CircPHLPP2 was initially identified through circRNA microarray analysis. Its expression in colorectal cancer patients and correlation with clinical parameters were evaluated by RT-qPCR. To determine its functional role, cell proliferation and colony formation assays, in vivo subcutaneous tumor models, and multicolor flow cytometry were conducted. Downstream signaling pathways influenced by circPHLPP2 were investigated using RNA sequencing, RT-qPCR, and Western blot analyses. Finally, RNA pull-down, RNA immunoprecipitation (RIP), and immunofluorescence assays were employed to uncover proteins interacting with circPHLPP2.CircPHLPP2 is upregulated in colorectal cancer patients who display resistance to anti-PD-1 therapy. It markedly promotes CRC cell proliferation and tumor growth, whereas silencing circPHLPP2 enhances the therapeutic effect of anti-PD-1 in vivo. Mechanistically, circPHLPP2 directly interacts with ILF3, promoting its accumulation in the nucleus and subsequently increasing IL36γ transcription. This cascade diminishes NK cell infiltration and suppresses their IFN-γ production and granzyme B, ultimately facilitating tumor progression.In summary, our study uncovers a previously unrecognized mechanism through which a circRNA mediates immune evasion in colorectal cancer. CircPHLPP2 holds potential as both a therapeutic target and a prognostic biomarker for CRC patients.
UR  - https://smerpub.com/article/circphlpp2-facilitates-colorectal-cancer-progression-and-anti-pd-1-resistance-via-ilf3-mediated-regu-xobmw30xdtqdnhg
ER  -