Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7

• Published in: Stem cell research & therapy Vol. 12; no. 1; p. 349
• Main Authors: Zhang, Ruijie, Li, Peng, Lv, Heli, Li, Nana, Ren, Suliang, Xu, Wentao
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16-06-2021; BioMed Central; BMC
• Subjects: Adult; Analysis; Antibodies; Apoptosis; Brain cancer; Brain tumors; c-Myc protein; Cancer; Care and treatment; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell Proliferation; Central nervous system; CSC; Development and progression; DNA microarrays; Exosome; Exosomes; Gene Expression Regulation, Neoplastic; Gene therapy; Genetic aspects; Glioma; Glioma - genetics; Glioma cells; Gliomas; Health aspects; Humans; Immunofluorescence; Medical prognosis; Myc protein; MyD88 protein; Neoplastic Stem Cells - metabolism; NF-κB protein; Non-coding RNA; Proteins; RNA; RNA, Long Noncoding - genetics; Signal transduction; SNHG16; Stem cells; TLR7; TLR7 protein; Toll-Like Receptor 7 - genetics; Toll-like receptors; Tumorigenesis; Wound healing; Xenografts; United States > US; China; SNHG16; CSC; TLR7; Glioma; Exosome
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-021-02393-8

Glioma is one of the most common central nervous system malignant tumors, accounting for 45~60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy.
Long non-coding RNA (lncRNA) SNHG16 expression level was measured by microarray and qRT-PCR assay; ISH was used to identify the location of SNHG16. Cancer stem cells (CSCs) were separated from glioma tissues and identified using immunofluorescence. Exosomes were isolated from CSCs and cancer cells and identified by TEM and western blot. MTT, wound healing, transwell, and colony formation assay were performed to explore the role of SNHG16 or si-SNHG16 from CSCs on progression of glioma cells. RIP was used to verify the interaction between SNHG16 and TLR7. The experiment of Xenograft used for exploring the function of SNHG16/ TLR7/MyD88/NFκB/c-Myc on growth on glioma in vivo.
Microarray assay showed long non-coding RNA (lncRNA) SNHG16 was upregulated in glioma. Followed qRT-PCR also showed an increase of SNHG16 in glioma tissues; high expression of SNHG16 indicated a poor prognosis in glioma patients. Interestingly, SNHG16 was packaged into exosomes and derived from CSCs. Functional analysis showed exo-SNHG16 secreted by CSCs promoted the progression of glioma cell lines SHG44 and U251. Furthermore, SNHG16 interacted with TLR7 and activated NFκB/c-Myc signaling in glioma cells. And the silencing of TLR7 inhibited the progression of SHG44 and U251 cells by exo-SNHG16 from CSCs. In vivo tumorigenesis experiments showed that exo-SNHG16 induced glioma progression by activating TLR7/MyD88/NFκB/c-Myc signaling.
Our study suggested CSC-derived exo-SNHG16 promoted cancer progression by activating TLR7/MyD88/NFκB/c-Myc signaling pathway.