miR-423-5p contributes to a malignant phenotype and temozolomide chemoresistance in glioblastomas

Abstract

Background Gliomas are based on a genetic abnormality and present with a dismal prognosis. MicroRNAs (miRNAs) are considered to be important mediators of gene expression in glioma tissues. Methods Real-time PCR was used to analyze the expression of microRNA-423-5p (miR-423-5p) in human glioma samples and normal brain tissue. Apoptosis, cell cycle, proliferation, immunostaining, transwell, in vitro 2D and 3D migration, and chemosensitivity assays were performed to assess the phenotypic changes in glioma cells overexpressing miRNA-423-5p. Western blotting was used to determine the expression of inhibitor of growth 4 (ING-4)in glioma tissues, and a luciferase reporter assay was conducted to confirm whether ING-4 is a direct target of miR-423-5p. Western blotting was used to identify the potential signaling pathways that are affected in glioma cell growth by miR-423-5p. Xenograft tumors were examined in vivo for the carcinogenic effects of miR-423-5p in glioma tissues. Results We first reported that miR-423-5p expression was increased in gliomas and was a potential tumor promoter via targeting ING-4. The overexpression of miR-423-5p resulted in upregulation of important signaling molecules such as p-AKT and p-ERK1/2. In clinical samples, miR-423-5p was dysregulated, and a corresponding alteration in ING-4 expression was observed (P = .0207). Furthermore, the overexpression of miR-423-5p strengthened glioma cell proliferation, angiogenesis, and invasion. Finally, miR-423-5p overexpression also strengthened GBM neurosphere formation and rendered glioma cells resistant to temozolomide (TMZ). Conclusion This study establishes that miR-423-5p functions as an oncogene in glioma tissues by suppressing ING-4 and suggests that it has therapeutic potential for glioma.

Retracted - miR-423-5p knockdown enhances the sensitivity of glioma stem cells to apigenin through the mitochondrial pathway

“…26 In gliomas, miR-423-5p is reportedly overexpressed in Chinese primary glioblastomas 27 and contributes to the malignant phenotype as well as TMZ chemoresistance. 11 However, the expression and function of miR-423-5p in GSCs have remained unknown. In this study, we confirmed that miR-423-5p is overexpressed in primary GSCs compared with corresponding primary glioma tissues.…”

miR-423-5p Inhibits Osteosarcoma Proliferation and Invasion Through Directly Targeting STMN1

“…For example, Li et al [38] showed that miR-423-5p expression was increased in gliomas tissues and ecoptic expression of miR-423-5p increased glioma cell angiogenesis, proliferation and invasion through targeting ING-4. Lu et al [39] demonstrated that serum miR-423-5p was upregulated in the stage I-II colorectal cancer patients compared with the control.…”

Exosomal miR‐423‐5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer

“…MiR‐423‐5p is previously reported to be aberrantly expressed in several cancers and could promote the proliferation and invasion of gastric cancer cells by downregulating the expression of trefoil factor 1 (TFF1) . However, whether miR‐423‐5p is enriched in the circulating exosomes of gastric cancer patients and the functional roles of exosomal miR‐423‐5p in gastric cancer have not been well characterized.…”