E2F transcription factor 1/small nucleolar RNA host gene 18/microRNA-338-5p/forkhead box D1: an important regulatory axis in glioma progression

Abstract

This study aims to probe the biological functions of long non-coding RNA small nucleolar RNA host gene 18 (SNHG18) on glioma cells and its underlying mechanism. In this study, SNHG18 expression in glioma tissues was quantified employing GEPIA database; quantitative real-time PCR was adopted to examine the expressions of SNHG18, microRNA-338-5p (miR-338-5p) and forkhead box D1 (FOXD1) mRNA in glioma tissues and cell lines; cell proliferation, migration and invasion were detected utilizing cell counting kit-8, EdU and Transwell assays; Western blot was utilized to quantify the protein expressions of E-cadherin, N-cadherin, Vimentin and FOXD1; dual-luciferase reporter gene and RNA immunoprecipitation experiments were utilized to validate the targeting relationships between SNHG18 and miR-338-5p, as well as miR-338-5p and FOXD1 mRNA 3ʹUTR; dual-luciferase reporter gene and chromatin immunoprecipitation assays were utilized to verify the binding of E2F transcription factor 1 (E2F1) to the SNHG18 promoter region. It was revealed that, SNHG18 expression in glioma was up-regulated and associated with unfavorable prognosis of the patients; knockdown of SNHG18 repressed the malignant biological behaviors of glioma cells, enhanced E-cadherin expression and repressed N-cadherin and Vimentin expressions. MiR-338-5p was a target of SNHG18, and SNHG18 promoted the expression of FOXD1 by decoying miR-338-5p. Additionally, E2F1 could bind to the promoter of SNHG18 to elevate its expression. In conclusion, SNHG18 accelerates glioma progression via regulating the miR-338-5p/FOXD1 axis.

Small nucleolar RNA host gene 18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia

“…It has been previously reported that SNHG18 is transactivated by megakaryocytic leukaemia 1 in non-small cell lung cancers 33 and E2F transcription factor 1 in glioma. 75 However, our unpublished data showed that none of these were impacted in serum-starved VSMCs by TGFβ1 treatment. Instead, we confirmed a critical role for Sp1 in SNHG18 transcriptional regulation in VSMCs.…”

“…Another study showed that SNHG18 accelerates glioma progression by regulating the miR-338-5p/FOXD1 (forkhead box D1) axis. 75 Similarly, it has been reported that SNHG18 facilitates non-small cell lung cancer growth and metastasis by modulating the miR-211-5p/BRD4 (bromodomain-containing protein 4) axis. 33 Conversely, SNHG18 has been suggested as a tumour suppressor and potential diagnostic biomarker in hepatocellular carcinoma.…”

“…Functioning as a competing endogenous RNA to regulate other RNA transcripts including miRNAs is one of the key mechanisms through which lncRNAs regulate cellular functions and disease pathogenesis. Indeed, previous studies in cancers have shown that SNHG18 promotes FOXD1 expression by decoying miR-338-5p, 75 suppresses nucleocytoplasmic transport of α-enolase, 32 and inhibits semaphorin 5A 31 in glioma cells. Moreover, SNHG18 exerts its prometastatic effects on non-small cell lung cancer cells through repression of miR-211-5p and induction of BRD4.…”

Aberrantly expressed long noncoding RNAs as potential prognostic biomarkers in newly diagnosed multiple myeloma: A systemic review and meta‐analysis

“… 80 Meanwhile, high expression of H19 leads to vincristine resistance in MM patients, in turn leading to poor prognosis. 50 SNHG18 promotes cell proliferation and metastasis in glioma 81 and nonsmall‐cell lung cancer. 82 It is also associated with poor prognosis in MM, 47 but the underlying mechanism remains unclear.…”