Increased level of H19 long noncoding RNA promotes invasion, angiogenesis, and stemness of glioblastoma cells

Abstract

OBJECTIVE Increased levels of H19 long noncoding RNA (lncRNA) have been observed in many cancers, suggesting that overexpression of H19 may be important in the development of carcinogenesis. However, the role of H19 in human glioblastoma is still unclear. The object of this study was to examine the level of H19 in glioblastoma samples and investigate the role of H19 in glioblastoma carcinogenesis. METHODS Glioblastoma and nontumor brain tissue specimens were obtained from tissue obtained during tumor resection in 30 patients with glioblastoma. The level of H19 lncRNA was detected by real-time quantitative reverse transcription polymerase chain reaction. The role of H19 in invasion, angiogenesis, and stemness of glioblastoma cells was then investigated using commercially produced cell lines (U87 and U373). The effects of H19 overexpression on glioblastoma cell invasion and angiogenesis were detected by in vitro Matrigel invasion and endothelial tube formation assay. The effects of H19 on glioblastoma cell stemness and tumorigenicity were investigated by neurosphere formation and an in vivo murine xenograft model. RESULTS The authors found that H19 is significantly overexpressed in glioblastoma tissues, and the level of expression was associated with patient survival. In the subsequent investigations, the authors found that overexpression of H19 promotes glioblastoma cell invasion and angiogenesis in vitro. Interestingly, H19 was also significantly overexpressed in CD133 glioblastoma cells, and overexpression of H19 was associated with increased neurosphere formation of glioblastoma cells. Finally, stable overexpression of H19 was associated with increased tumor growth in the murine xenograft model. CONCLUSIONS The results of this study suggest that increased expression of H19 lncRNA promotes invasion, angiogenesis, stemness, and tumorigenicity of glioblastoma cells. Taken together, these findings indicate that H19 plays an important role in tumorigenicity and stemness of glioblastoma and thus could be a therapeutic target for treatment of glioblastoma in the future.

Expression of the long non‐coding RNA H19 and MALAT‐1 in growth hormone‐secreting pituitary adenomas and its relationship to tumor behavior

“…LncRNA H19 participates in cancer cell proliferation, migration, invasion and metastasis. In recent studies, lncRNA‐H19 revealed two opposite function according to tumor types, one effect of lncRNA‐H19 is as an oncogene in breast cancer (Collette et al, 2017), colorectal cancer (Liang et al, 2017), glioblastoma (Jiang et al, 2016), and ovarian cancer (Medrzycki et al, 2014), the other one effect of lncRNA H19 is as a tumor suppressor in hepatocellular carcinoma (Lv et al, 2014), Wilms' tumors (Yoshimizu et al, 2008) and prostate cancer (Zhu et al, 2014). In this study, the expression of lncRNA H19 is remarkably higher in invasive GHPAs, suggesting that lncRNA H19 may play an important role in GHPA invasion.…”

Huaier Extract Inhibits Breast Cancer Progression Through a LncRNA-H19/MiR-675-5p Pathway

“…An increasing number of lncRNAs have been identified as playing critical roles in cancer development and progression [43-45]. LncRNA H19 is located on the 11p15.5 locus and functions as an oncogene in several cancers [46-48]. Here, we initially analyzed lncRNA microarray profiles to identify candidate lncRNAs associated with the cytotoxic role of Huaier extract.…”

Down‐regulated lncRNA HOTAIR alleviates polycystic ovaries syndrome in rats by reducing expression of insulin‐like growth factor 1 via microRNA‐130a

“…LncRNA profiles in granulosa cells from patients with PCOS and healthy women demonstrate that dysregulated lncRNAs may play significant roles in steroidogenesis and granulosa cell proliferation, shedding lights on the aetiology of PCOS . LncRNAs have emerged as important epigenetic mediators with critical functions in the development and disease . HOTAIR is a 2158 bp lncRNA localised to a boundary in the HOXC gene cluster .…”