<p>MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin</p>

Abstract

Purpose: Several microRNAs (miRNAs) that are aberrantly expressed in glioblastoma multiforme (GBM) play a significant role in GBM formation and progression. The expression profile and functions of miR-559 in GBM remain unclear. Here, we quantified the expression and investigated the involvement of miR-559 in the oncogenicity of GBM cells in vitro and in vivo. Material and methods: Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was carried out to determine miR-559 expression in GBM tissues and cell lines. A series of functional assays was performed to evaluate the effects of miR-559 overexpression on GBM cell proliferation, apoptosis, migration, and invasion in vitro and on GBM tumor growth in vivo. The regulatory mechanisms of miR-559 action in GBM cells were then explored. Results: The expression of miR‑559 was lower in GBM tissues and cell lines and significantly correlated with the Karnofsky performance score and tumor size among patients with GBM. Exogenous miR‑559 expression inhibited GBM cell proliferation, migration, and invasion and promoted apoptosis. MiR-559 overexpression decreased tumor growth in vivo. Mechanistic experiments confirmed metadherin ( MTDH ) as a direct target gene of miR-559 in GBM. Silencing of MTDH induced effects similar to those of miR-559 upregulation in GBM cells, whereas MTDH expression restoration attenuated the antitumor effects of miR‑559 in GBM cells. Protein kinase B (AKT) in the phosphatase and tensin homolog (PTEN)–AKT signaling pathway was found to be deactivated in GBM cells after upregulation of miR-559 both in vitro and in vivo. Conclusion: MiR-559 acts as a tumor suppressor in GBM cells in vitro and in vivo, at least in part through the downregulation of MTDH and inhibition of AKT in the PTEN–AKT pathway. Therefore, targeting the miR-559–MTDH axis may be a promising therapeutic strategy for patients with GBM.

MiR‐559 targets GP73 to suppress proliferation and invasion of hepatocellular carcinoma in vitro

“…22 Chen and his colleagues revealed that miR-559 and miR-548d-3p could synergistically inhibit the expression of the oncogene ERBB2. 23 Yang et al 9 reported that miR-559 function as a tumor suppressor in glioblastoma multiform, and its inhibitory effect was related to metadherin and PTEN-AKT pathway. In our current investigation, we found that miR-559 was associated with HCC, and ectopic expression of miR-559 could inhibit HCC cell proliferation and migration.…”

“…For instance, miR‐200b suppressed HCC cell proliferation and migration by targeting HMGB3 7 whereas upregulated miR‐130a enhanced drug resistance of HCC via downregulating RUNX3 expression and activating Wnt/β‐catenin signaling 8 . MiR‐559 is a novel miRNA that can inhibit the progression of glioblastoma 9 . However, the expression pattern and function of miR‐559 in HCC remains unclear.…”

“…8 MiR-559 is a novel miRNA that can inhibit the progression of glioblastoma. 9 However, the expression pattern and function of miR-559 in HCC remains unclear.…”

MicroRNA-559 restrains gastric cancer progression via activating AKT signaling pathway by targeting TRIM14

“…Up to date, a few researches discover that miR-559 is clinical implication and acts as an important role in breast cancer, papillary thyroid carcinoma and glioblastoma [15][16][17]. Whereas, the effect and molecular mechanism of miR-559 in GC carcinogenesis and progression is still unclear and demand to be further illuminated.…”

“…Abnormity of miR-559 has been reported for several different cancers. Even though recent evidences demonstrated the inhibitory effect of miR-559 on human cancers, such as breast cancer, papillary thyroid carcinoma and glioblastoma[16,17], the functions of miR-559 in GC and the underlying mechanisms are still unknown. In this study, it was found that the expression of miR-559 was remarkably downregulated in both GC tissues and cell lines.…”