miR‑296‑3p promotes the proliferation of glioblastoma cells by targeting ICAT

Abstract

Micrornas (mirna/mirs) serve an important function in the regulation of gene expression, and have been indicated to mediate a number of cellular biological processes, including cell proliferation, the cell cycle, cell apoptosis and cell differentiation. The altered expression of mirnas has been revealed to result in a variety of human diseases, including glioblastoma multiforme (GBM). The present study indicated an increase in mir-296-3p in glioma tumor types compared with normal brain, particularly in the samples from patients with high grade GBM. antagonizing mir-296-3p was demonstrated to induce cell growth arrest and cell cycle redistribution in u251 cells. The mir-296-3p antagonist altered the expression of a number of key genes that are involved in cell cycle control, including cyclin d1 and p21. additionally, the decrease of mir-296-3p increased inhibitor of β-catenin and T cell factor (icaT) expression, and increased mir-296-3p-inhibited icaT expression in u251 cells. Bioinformatics analysis indicated that icaT is a target gene of mir-296-3p, which was further validated using a dual-luciferase reporter assay. Through the regulation of icaT, the mir-296-3p antagonist decreased β-catenin protein expression and increased the expression of its target genes. Silencing icaT was indicated to reverse the mir-296-3p downregulation-induced inactivation of Wnt signaling and cell growth arrest in glioma cells. The present study also indicated a negative correlation between icaT mrna levels and mir-296-3p levels in glioma tumor types. In conclusion, the present study identified an oncogenic function of mir-296-3p in glioblastoma via the direct regulation of icaT.

Extracellular vesicle‐encapsulated microRNA‐296‐3p from cancer‐associated fibroblasts promotes ovarian cancer development through regulation of the PTEN/AKT and SOCS6/STAT3 pathways

“…Previous studies have shown that miR‐296‐3p is dysregulated in various tumors, where it can promote or inhibit tumor progression by targeting different genes 18 . For example, miR‐296‐3p has been shown to be upregulated in prostate cancer and glioma and promoted tumor proliferation and metastasis by targeting ICAM‐1 and ICAT, respectively 19,33 . In contrast, miR‐296‐3p has also been reported to function as tumor suppressor and inhibited cell proliferation, metastasis, and drug resistance in lung cancer by targeting PRKCA 34 .…”

Circular RNA circHECTD1 facilitates glioma progression by regulating the miR‐296‐3p/SLC10A7 axis

“…Lee et al reported that miR‐296‐3p may be regulated by neurofibromatosis 2, and it enhances the invasion capacity of GBM cells via SOCS2/STAT3 (Lee et al, 2016). Similarly, J. Zhou et al (2020) have presented a study indicating an oncogenic role of miR‐296‐3p in glioblastoma via regulating ICAT. With bioinformatics analysis, the target sites of circHECTD1 were detected in the miR‐296‐3p; therefore, we speculated that circHECTD1 may interact with miR‐296‐3p in glioma.…”

“…Similarly, J. Zhou et al (2020) have presented a study indicating an oncogenic role of miR-296-3p in glioblastoma via regulating ICAT. With bioinformatics analysis, the target sites of circHECTD1 were detected in the miR-296-3p; therefore, we speculated that circHECTD1 may interact with miR-296-3p in glioma.…”

Recent insights into the microRNA-dependent modulation of gliomas from pathogenesis to diagnosis and treatment

“…More interestingly, the expression of ICAT can be modulated by different miRNAs in various different types of cancer, including hepatocellular carcinoma (HCC), breast cancer, and GBM [ 115 , 116 ]. On the other hand, miR-296-3p is also downmodulated in GBM tissues compared to normal brain [ 117 ].…”