HOTAIRM1 Promotes Malignant Progression of Transformed Fibroblasts in Glioma Stem-Like Cells Remodeled Microenvironment via Regulating miR-133b-3p/TGFβ Axis

Abstract

Recent studies have reported that cancer associated fibroblasts (CAFs) and glioma stem-like cells (GSCs) played active roles in glioma progression in tumor microenvironment (TME). Long non-coding RNAs (lncRNAs) have been found to be closely associated with glioma development in recent years, however, their molecular regulatory mechanisms on CAFs in GSCs remodeled TME kept largely unelucidated. Our study found that GSCs could induce malignant transformation of fibroblasts (t-FBs) based on dual-color fluorescence tracing orthotopic model. Associated with poor prognosis, Lnc HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1) was highly expressed in high-grade gliomas and t-FBs. Depleting HOTAIRM1 inhibited the proliferation, invasion, migration, and even tumorigenicity of t-FB. Conversely, overexpression of HOTAIRM1 promoted malignancy phenotype of t-FB. Mechanistically, HOTAIRM1 directly bound with miR-133b-3p, and negatively regulated the latter. MiR-133b-3p partly decreased the promotion effect of HOTAIRM1 on t-FBs. Furthermore, transforming growth factor-β (TGFβ) was verified to be a direct target of miR-133b-3p. HOTAIRM1 can modulate TGFβ via competing with miR-133b-3p. Collectively, HOTAIRM1/miR-133b-3p/TGFβ axis was involved in modulating t-FBs malignancy in TME remodeled by GSCs, which had the potential to serve as a target against gliomas.

Identification and targeting of G-quadruplex structures inMALAT1long non-coding RNA

“…As described early in the result section, we have re-analyzed and identified more than 350 rG4 in about 200 ncRNAs using our published rG4-seq dataset. In this list (Table S1), we also found rG4s in other biologically relevant lncRNAs such as TUG1 (taurine upregulated gene 1), HCG11 (HLA Complex Group 11), DGCR5 (DiGeorge Syndrome Critical Region Gene 5), HOTAIRM1 (HOXA Transcript Antisense RNA, Myeloid-Specific 1), and many more, which have been functionally characterized in other studies recently (92)(93)(94)(95)(96)(97)(98)(99). Our view is that this list is likely an underestimation of the rG4s in ncRNAs as the rG4-seq was polyAenriched (5), and many lncRNAs do not have polyA tail or polyA region, which will be omitted in the dataset.…”

GAS5 Attenuates Malignant Progression of Glioma Stem-like Cells via Regulating E-cadherin

“…Other upper chambers were pre-coated with Matrigel (50µl, 1:100 dilution) for migration assays, in which the Matrigel was aspirated after 20min. The subsequent protocol was performed as previously described 14 .…”

Breaking Bad: Autophagy Tweaks the Interplay Between Glioma and the Tumor Immune Microenvironment

“…And this pro-invasive effect brought by CAFs in glioma could also be mediated by the secretion of CXCL14 ( 126 ). Furthermore, it reveals that long non-coding RNA (lncRNA) HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1), is upregulated in the malignantly transformed fibroblasts derived from an orthotopic model and regulates TGF-β via miR-133b-3p to promote malignancy ( 127 ).…”