Abstract 2360: Identifying differentially expressed miRNAs in CRC stem cell subpopulations

Our research goal is to discover the molecular mechanisms behind tumor heterogeneity in CRC. We previously showed that CRCs contain multiple subpopulations of cancer stem cells (CSCs) which may explain the occurrence tumor heterogeneity and resistance to treatment. To determine how CSC sub-populations might arise, we are studying miRNA expression in CRC SCs. MicroRNAs are known to regulate SC phenotype and are found to be dysregulated in many cancers. Hypothesis: Tumor heterogeneity results from existence of multiple CSC subpopulations that are regulated by distinct miRNAs. Accordingly, we are using bioinformatics and miRNA profiling to identify miRNAs that target SC genes in CRCs. Indeed, our miRNA expression profiling of normal and malignant ALDH+ human colonic SCs showed that miRNA92a targets the SC gene LRIG1 and upregulation of miRNA92a leads to decreased LRIG1 expression. We also discovered that miRNA23b targets the SC gene LGR5 and miRNA23b is upregulated in ALDH+ CSCs. We have identified several other candidate miRNAs that are predicted to target CD166, ALDH1A1, BMI1, LRG5, and LRIG1 SC genes. We are currently in the process of validating whether these miRNAs contribute to emergence of specific CSC sub-populations in CRCs. Thus, identifying miRNAs that regulate CSC subpopulations should provide new strategies to modulate CSC composition in order to sensitize tumors to treatments. Citation Format: Victoria A. Stark, Vignesh Viswanathan, Caroline O. Facey, Lynn M. Opdenaker, Bruce M. Boman. Identifying differentially expressed miRNAs in CRC stem cell subpopulations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2360.