miR-221/222 promote malignant progression of glioma through activation of the Akt pathway

Abstract

Abstract. MicroRNAs (miRNAs) are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional level. Emerging evidence suggests that miRNAs play important roles in the pathogenesis of several types of cancers. However, the further mechanisms of miRNA remain unknown. In this study, we aimed to explore the coordinated function of miR-221/222 in glioma by bioinformatics and experiment methods. Bioinformatics analysis revealed that miR-221/222 had the potential to regulate about 70 common target genes and may exert a cooperative effect on regulation and function via Akt signaling pathway. Overexpression of miR-221/222 increased glioma cell proliferation and invasion in vitro and induced glioma growth in a subcutaneous mouse model. Furthermore, miR-221/222 overexpression resulted in an obvious activation of p-Akt and significant changes of Aktrelated gene expression in glioma cells. Our results suggest that miR-221/222 co-enhance the glioma malignant phenotype via activation of the Akt pathway mediated by regulation of common gene expression.

Identification and Potential Mechanisms of a 7-MicroRNA Signature That Predicts Prognosis in Patients with Lower-Grade Glioma

“…Moreover, the downregulation of hsa-miR-10b-5p repressed spread, movement, and invasion of glioma cell by the activation of TGF- β 1 stimulation [ 31 ] or homeobox B3 (HOXB3) expression [ 39 ]. For hsa-miR-221-3p, researchers discovered the overexpression could activate the Akt pathway [ 40 ]. Though there are few studies analyzing the expression and function of the hsa-miR-3200-3p and hsa-miR-548b-3p in LGG, the hsa-miR-3200-3p and hsa-miR-548b-3p have been reported to inhibit growth, migration, and invasion of tumor cells of the gastrointestinal tract and hepatocellular carcinoma cells separately [ 41 , 42 ].…”

Clinical Impact of Oncomirs 221 and 222 on Breast Cancer Diagnosis

“…Several recent studies have demonstrated that miRNAs are stably detectable in plasma/serum [28,29,30]. MiRNA-221 and miRNA-222 are overexpressed in different types of malignant neoplasms including ovarian cancer 31, hepatocellular cancer [32], glioblastomas [33] and breast cancer [10,13,34]. Both miRNAs were shown to promote cell growth, cell cycle progression and invasion in these tumore types in vitro and in vivo [32,33].…”

Neuroendocrine mechanism of gastric acid secretion: Historical perspectives and recent developments in physiology and pharmacology

“…Gastrin is known to induce miR‐222 overexpression, 70 which has been reported to be upregulated in many types of cancer 71–74 . Higher levels of miR‐222 are associated with more advanced disease and reduced 5‐year survival 75,76 .…”

“…69 Gastrin is known to induce miR-222 overexpression, 70 which has been reported to be upregulated in many types of cancer. [71][72][73][74] Higher levels of miR-222 are associated with more advanced disease and reduced 5-year survival. 75,76 miR-222 expression is also increased in gastric cancer tissue-derived mesenchymal stem cells and in the stomach of H. pylori infected individuals.…”