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 and RNA immunoprecipitation assays 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 the miR-20b-5p/PD-L1 axis. Conclusion:HCG18 facilitated progress of the tumor, conferred to cetuximab resistance and suppressed CD8+ T cells via the miR-20b-5p/PD-L1 axis.
Keywords: CD8+ T cell; PD-L1; cetuximab; colorectal cancer; lncRNA HCG18; miR-20b-5p.
Lay abstract In the present study, we found a long noncoding RNA (lncRNA), HCG18 (a recently discovered lncRNA that facilitates tumor progression via multiple mechanisms), was upregulated in colorectal cancer (CRC). Further studies 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 suppressing the proliferation of CD8+ cytotoxic T lymphocytes) via sponging (lncRNA binds with miRNA) miR-20b-5p. This study might provide a deeper insight into understanding cetuximab resistance in CRC.