Abstract P6-07-03: Long non-coding RNA H19 promotes cancer stemness and worsen breast cancer survival

Background : Cancer stem cells (CSC) are good sources of tumor initiation, heterogeneity, progression, and metastasis because of their unique characteristics. Several potential markers for CSCs have been suggested for breast cancer, including CD44 + /CD24 −/low , aldehyde dehydrogenase 1 (ALDH1), and epithelial cell adhesion molecule/epithelial-specific antigen. We previously reported that ALDH1 gene expression is related to aggressive phenotypes and poor prognosis in breast cancers. In this study, we conducted differential analysis of mRNA expression in ALDH1-positive breast cancer to identify genes associated with CSC. Next, we performed basic and clinical studies of one gene. Methods : Messenger RNA was isolated from ALDH1-positive cells and ALDH1-negative cells in 5 ALDH1-positive breast cancers. Microarray analysis revealed that several genes were significantly associated with the ALDH1 gene. Among them, we examined a long non-coding RNA of H19 in this study. We evaluated the effect of H19 on CSCs using RNA interference and a sphere formation assay using two cell lines, HCC1937 and iCSCL10A cells. We also investigated H19 expression in 192 surgical specimens by in situ hybridization and analyzed the relationship between H19 expression and clinic pathological findings in breast cancer patients. Results : Through in vitro experiments, we confirmed that suppression of H19 reduced sphere formation in both HCC1937 and iCSCL10A cells. Among surgical specimens, 48 samples (25%) expressed H19. We verified thatH19 positivity was significantly higher in ALDH1-positive cases than in ALDH1-negative cases (68% vs 9.7%, p Conclusions : H19 is clearly associated with CSCs and correlated with poor prognosis in breast cancer patients, particularly TNBC. Our future studies will investigate the role of H19 in maintaining the nature of CSCs and protein-coding genes associated with H19. Citation Format: Shima H, Kida K, Yamada A, Sugae S, Narui K, Miyagi Y, Ryo A, Ichikawa Y, Ishikawa T, Endo I. Long non-coding RNA H19 promotes cancer stemness and worsen breast cancer survival [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-07-03.