Glioblastoma (GBM) belongs to the high‐grade (IV) gliomas with extremely poor prognosis. Accumulating evidence uncovered the key roles of long non‐coding RNAs (lncRNAs) in GBM development. This study aimed to determine the biological actions and the clinical relevance of lncRNA MIR4435‐2 Host Gene (MIR4435‐2HG) in GBM. Data from GEPIA database showed that MIR4435‐2HG was up‐regulated in GBM tissues and high expression of MIR4435‐2HG correlated with shorter overall survival of GBM patients. Further experimental assays verified the up‐regulation of MIR4435‐2HG in GBM tissues and cell lines. In vitro cell studies and in vivo animal studies showed that knockdown of MIR4435‐2HG resulted in the inhibition of GBM cell proliferation and invasion and in vivo tumour growth, while MIR4435‐2HG overexpression driven GBM progression. Furthermore, MIR44435‐2HG was found to sponge miR‐1224‐5p and suppress miR‐1224‐5p expression; overexpression of miR‐1224‐5p attenuated the enhancement in GBM cell proliferation and invasion induced by MIR4435‐2HG overexpression. In a subsequent study, miR‐1224‐5p was found to target transforming growth factor‐beta receptor type 2 (TGFBR2) and repressed TGFBR2 expression, and in vitro assays showed that miR‐1224‐5p exerted tumour‐suppressive effects via targeting TGFBR2. More importantly, TGFRB2 knockdown antagonized hyper‐proliferation and invasion of GBM cells with MIR4435‐2HG overexpression. Clinically, the down‐regulation of miR‐1224‐5p and up‐regulation of TGFBR2 were verified in the GBM clinical samples. Taken together, the present study suggests the oncogenic role of MIR4435‐2HG in GBM and underlies the key function of MIR4435‐2HG‐driven GBM progression via targeting miR‐1224‐5p/TGFBR2 axis.
This study investigates the expression of hypoxia-inducible factor-l alpha (HIF-1α) and carbonic anhydrase IX (CAIX) in nasopharyngeal carcinoma (NPC) tissues and their correlation with clinicopathological features and prognosis in NPC patients. The expression of HIF-1α and CAIX proteins was detected by immunohistochemical staining in 129 samples of NPC and 20 samples of chronic nasopharyngitis. The correlations between the expression of these two proteins and clinicopathological features and prognosis were evaluated in NPC patients. Our results showed that the positive expression rates of HIF-1α and CAIX proteins in NPC were significantly higher than those in chronic nasopharyngitis (both P < 0.01). In addition, high HIF-1α protein expression was correlated with lymph node metastasis and advanced clinical stage for NPC patients (both P < 0.01), whereas there were no findings of correlations between CAIX protein expression and gender, age, T stage, node involvement and clinical stage (all P > 0.05). The Spearman analysis indicated that HIF-1α was positively correlated with CAIX expression (r = 0.249, P = 0.004). HIF-1α and CAIX co-expression was associated with the poor overall survival (OS), progression-free survival (PFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) in NPC patients (P = 0.017, P = 0.022, P = 0.033, and P = 0.017, respectively). Multivariate analysis showed that the positive expression of CAIX protein was an independent prognostic factor for PFS, LRRFS and DMFS. In conclusion, overexpression of HIF-1α and CAIX might be involved in the carcinogenesis and development of NPC and they were associated with patients’ poor prognosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.