LncRNA HCG18 suppresses CD8+ T cells to confer resistance to cetuximab in colorectal cancer via miR-20b-5p/PD-L1 axis

Lay abstract In present study, we found a long noncoding RNA (lncRNA), HCG18 (a recently discovered lncRNA that facilitate tumor progression via multiple mechanisms) was upregulated in colorectal cancer (CRC). Further study revealed that HCG18 suppressed CD8(+) T cell (cytotoxic T lymphocyte which kills cancer cell) activation to induce cetuximab (a first-line drug in CRC) resistance. Mechanically, HCG18 elevated expression of PD-L1 (a receptor in T cell membranes, thus suppressed proliferation of CD8(+) cytotoxic T lymphocyte) via sponging (lncRNA binds with miRNA) miR-20b-5p. This study might provide deeper insight to understanding cetuximab resistance in CRC. Aim: We aimed to explore the effect of long noncoding RNA HCG18 in colorectal cancer (CRC). Materials & methods: Relative gene and protein expression were screened. Colony formation and flow cytometry assays were performed to determine proliferation and apoptosis. Dual luciferase assay and RNA immunoprecipitation assay were conducted to validate the interaction between indicated molecules. Xenograft in nude mice was applied to verify the conclusion in vivo. Results: HCG18 and PD-L1 were upregulated while miR-20b-5p was downregulated in CRC tissue. Functional analysis revealed that lncRNA HCG18 promoted proliferation, migration and resistance to cetuximab of CRC cells via miR-20b-5p/PD-L1 axis. Conclusion: HCG18 facilitated the progress of tumor, conferred to cetuximab resistance and suppressed CD8(+) T cell via miR-20b-5p/PD-L1 axis.

Automated summary

In this study, a long noncoding RNA named HCG18 was found to be upregulated in colorectal cancer, promoting tumor cell proliferation, migration, and resistance to cetuximab through the regulation of the miR-20b-5p/PD-L1 axis. Additionally, HCG18 was shown to suppress the activation of CD8(+) T cells.