microRNA-205 acts as a tumor suppressor and directly targets YAP1 in glioma

Abstract

Glioma is the most common form of primary malignant tumor that occurs in the central nervous system. The underlying molecular mechanism of the carcinogenesis and progression of glioma remains to be elucidated. It is well‑established that microRNAs (miRs) are associated with the regulation of glioma initiation and progression, and may represent a novel effective therapeutic strategy for the treatment of glioma. In the present study, the expression, roles and molecular mechanisms of miR‑205 in glioma were investigated. The expression levels of miR‑205 in glioma tissues, normal brain tissues, human glioma and normal HEB glial cell lines were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). To explore the functional roles of miR‑205 in glioma cells, a Cell Counting kit 8 assay, and Transwell migration and invasion assays were employed. The molecular mechanisms underlying the roles of miR‑205 in glioma cells were investigated using bioinformatics analysis, a luciferase reporter assay, RT‑qPCR and western blot analysis. The results of the present study demonstrated that miR‑205 expression was markedly low in glioma tissues and cell lines compared with normal brain tissue and a glial cell line. Upregulation of miR‑205 in vitro decreased cell viability, migration and invasion in glioma. Further investigation of the potential molecular mechanism demonstrated that the tumor suppressive functions of miR‑205 in regulating the proliferation, migration and invasion of glioma cells were mediated by a direct target gene, yes associated protein 1 (YAP1). The results of the present study suggested that miR‑205 inhibited glioma growth and metastasis by directly targeting YAP1, and that miR‑205 should be investigated as a novel therapeutic target for anti‑cancer treatment.

miR-205: A Potential Biomedicine for Cancer Therapy

“…Yes Associated Protein 1 (YAP1) is a transcriptional regulator that plays a crucial role in regulating cellular proliferation and migration in cancer [ 168 ] and was identified as another direct target for miR-205 through bioinformatics analyses utilizing TargetScan and miRanda prediction tools [ 49 ]. A luciferase reporter assay demonstrated that miR-205 directly binds to the YAP1 gene at 3′ UTR and the overexpression of miR-205 significantly reduced the expression of this transcriptional factor at both gene and protein levels as confirmed by qRT-PCR and Western blotting analyses [ 49 ]. Considering the low levels of miR-205 in glioma and its association with cancer development, this miRNA may be utilized as a potent diagnostic biomarker and can also serve as a therapeutic target.…”

MicroRNA205: A Key Regulator of Cardiomyocyte Transition from Proliferative to Hypertrophic Growth in the Neonatal Heart

“…Interestingly, the PI(3)K/Akt pathway is central to the regulation of physiological hypertrophy in the heart [41][42][43]. However, what is most interesting is the observation that miR205 directly targets YAP1 [44] a key component of the Hippo pathway and a mediator of hyperplasia.…”

“…Based on these observations, we chose to examine whether there may be a functional intersection in the early perinatal heart between miR205 and the Hippo pathway. Yap, a direct target of miR205 [44], was dramatically upregulated in miR205 null hearts (Figure 2) with a corresponding increase in the expression and activity of CDK1 (Figure 2), a direct regulator of Yap [47][48][49], therefore supporting the concept that the temporal increase in mir205 during the first 7 days post-birth leads to targeted suppression of Yap-mediated cardiomyocyte proliferation and at the same time promoting the PI(3)K/Akt mediated hypertrophic pathway in cardiomyocytes.…”

Identification of FBXW7α-regulated genes in M1-polarized macrophages in colorectal cancer by RNA sequencing

“…Wang et al,13 demonstrated that miR-205 inhibits the development of renal cell carcinoma through regulating the PTEN/AKT pathway. Ji et al,14 reported that miR-205 functions by targeting Yap1 in glioma. Further, Zeng et al,8 found that miR-205 could repress SMAD4 expression in A549 cell lines, which was similar to our results.…”