LncRNA XIST knockdown suppresses the malignancy of human nasopharyngeal carcinoma through XIST/miRNA-148a-3p/ADAM17 pathway in vitro and in vivo - 30/11/19
, Yusheng Wang a, ⁎, 2Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Graphical abstract |
Expression of XIST and ADAM17 is upregulated, and miR-148a-3p is downregulated in human NPC tissues and cell lines. XIST-silenced CNE2 and SUNE-1 cells exhibit restrained tumor growth in vivo, and decreased cell proliferation, EMT, migration and invasion in vitro, but increased apoptosis. Mechanically, knockdown of XIST downregulated ADAM17 expression through sponging miR-148a-3p.
Highlights |
• | XIST knockdown suppressed the malignant behaviors of NPC cells in vitro and in vivo. |
• | Overexpression of miR-148a-3p inhibited NPC cell malignancy in vitro. |
• | XIST positively modulated ADAM17 expression via sponging miR-148a-3p. |
• | XIST/miR-148a-3p/ADAM17 pathway might contribute to NPC development. |
Abstract |
Background |
Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in human cancers, including nasopharyngeal carcinoma (NPC). However, the role of XIST in NPC remains to be largely uncovered, as well as its underlying mechanism.
Methods |
Expression of XIST, miR-148a-3p and ADAM17 was detected using qPCR and western blot assay. Cell proliferation and apoptosis assay were measured with MTT and flow cytometry, separately. Migration and invasion abilities were examined by transwell assays. Epithelial-mesenchymal transition (EMT) was assessed by western blot analyzing levels of E-cadherin, N-cadherin and vimentin. The potential binding between miR-148a-3p and XIST/ADAM17 was validated by luciferase reporter assay, Ago2-RNA immunoprecipitation and RNA pull-down assay. Xenograft experiments were conducted to measure tumor growth.
Results |
XIST was upregulated and miR-148a-3p was downregulated in NPC tissues and cell lines. Both XIST knockdown and miR-148a-3p overexpression promoted apoptosis, suppressed cell proliferation, migration, invasion, and EMT of NPC cells in vitro. In addition, miR-148a-3p was validated as a target of XIST, and silencing of miR-148a-3p could reverse XIST knockdown-mediated functions in SUNE-1 and CNE2 cells. Furthermore, miR-148a-3p was identified to target ADAM17, and ectopic expression of ADAM17 could abate miR-148a-3p-induced effects as well. Notably, ADAM17 was downregulated by XIST knockdown through upregulating miR-148a-3p. In vivo, XIST knockdown resulted in a slower tumor growth.
Conclusion |
Knockdown of XIST suppresses the malignant progression of NPC cells through targeting miR-148a-3p/ADAM17 axis both in vitro and in vivo.
Le texte complet de cet article est disponible en PDF.Keywords : XIST, miR-148a-3p, A disintegrin and metalloproteinase 17 (ADAM17), Nasopharyngeal carcinoma (NPC), Malignancy
Plan
Vol 121
Article 109620- janvier 2020 Retour au numéro
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