Abstract 2439: RPL27 augments growth and stemness properties in colorectal cancer through PLK1 signaling

Abstract

Abstract Background: In 2020, colorectal cancer (CRC) had the second highest mortality rate worldwide and was the third most common cancer type among various carcinomas, accounting for 10.0% and 9.4% of all carcinomas, respectively. Although the expression of ribosomal protein L27 (RPL27) is upregulated during CRC development, oncogenic roles of RPL27 have not yet been elucidated. We aimed in this study to investigate the effect of RPL27 targeting on CRC growth and whether RPL27 gained an extra-ribosomal function during CRC development. Methods: Human CRC cell lines, HCT116 and HT29, were transfected with RPL27-specific siRNA and tested for growth inhibition and apoptotic induction using MTS, FACS and Western blotting. To obtain insights into the molecular changes in response to RPL27 knockdown, global changes in gene expression were examined using RNA sequencing. Results: We observed that inhibition of RPL27 expression suppresses CRC cell growth and long-term colony formation through an induction of apoptotic cell death. Targeting RPL27 also significantly inhibited the growth of human CRC xenografts in nude mice. Noticeably, polo-like kinase 1 (PLK1), which is known to play an important role in mitotic cell cycle progression and stemness, was commonly down-regulated in both HCT116 and HT29 cells with RPL27 depletion. Western blot analysis confirmed that RPL27 silencing reduces the levels of PLK1 protein and G2/M-associated regulators, such as p-CDC25C, CDK1, and cyclin B1. Reflecting these molecular responses, knockdown of RPL27 reduced the migration and invasion abilities of CRC cells. In terms of CSC phenotypic changes, RPL27 knockdown suppressed sphere forming capacity of isolated CD133+ CSC population accompanying with the reduction in CD133 and PLK1 levels. Conclusion: Taken together, these findings indicate that RPL27 contributes to promotion of CRC growth and stemness through PLK1 signaling and that targeting RPL27 could be a next-line therapeutic strategy for both primary CRC treatment and prevention of metastasis and/or recurrence. Citation Format: Keon Uk Park, Ilseon Hwang, Hun Mo Ryoo, Yun-Han Lee, So-Young Park. RPL27 augments growth and stemness properties in colorectal cancer through PLK1 signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2439.