<p>MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin</p>
Authors: Fan Yang
Dong Han
Chuangang Zhang
Fangyou Fu
Hongliang Li
Congbin Xu
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: glioblastoma; metadherin; microRNA-559; oncogenicity; target therapy.
Affiliations: Department of Neurosurgery., Department of Oncology., Department of Radiology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, People's Republic of China., Department of Emergency, The People's Hospital of Linyi East Medical District, Linyi, Shandong 276000, People's Republic of China.

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. 

Retracted: Yes

PubPeer comments:
 Figs 2C, 4C, 5C. ![file] Brown-boxed panel also appears in Figs 2C, 4C, 5C of [Li et al (2019)] . ![file] Here in context. ![file] There may be other matches, or matches with other papers from this same oeuvre. , 
 Clockwise from upper left: - Fig 9A from [Pang et al (2019)] .  A representative image of the [BGC-823] tumor xenografts obtained from the agomir-628 and agomir-NC groups. Rotated through 90 deg to facilitate comparison. - Fig 7B from [Yan et al (2019)] again.  The representative images of the [HCT116] tumor xenografts obtained from the agomir-629 group and the agomir-NC group. - **Fig 7A from [Yang et al (2019)] **.  Representative images of the tumor xenografts 4 weeks after inoculation with U251 cells expressing miR-559 mimics or miR-NC. Rotated through 90 deg. - Fig 8A from [Li, Li Sun (2019)] .  Photographs of tumor xenografts derived from agomir-876u2013 and agomir-NCu2013 transfected MCF-7 cells . ![file] Some pairs of tumors are more similar than one would expect, as if they are the same tumors with slightly different lighting. All four institutions seem to be using **the same ruler**, distinguished by a scrape just to the left of the 1 . Do they pass it around, like the single eye and the single tooth of the Graeae? UPDATE: Another sighting of the ruler! Fig 7A from [Li et al (2019)] ,  Representative images of tumor xenografts derived from HOS cells transfected with the miR-618 mimics or miR-NC . Rotated through 90 deg. ![] , 
 Retracted, [22 September 2021] . --------------------------------- The Editor and Publisher of *OncoTargets and Therapy* wish to retract the published article. Concerns were raised over alleged image duplication in Figures 5C and 7A with similar images from unrelated articles, specifically: - Figure 5C, panel T98 miR-NC appears to have been duplicated with a similar image in Figure 4C from Li et al, 2019 . - Figure 7A, appears to have been duplicated with similar images in Figure 8A from Li et al, 2019 . The authors did not respond to our queries and the Editor determined the findings of the study were no longer valid and advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. , 
 Fig 5D E: ![] Fig 4C D from  Long Noncoding RNA FOXD2-AS1 Promotes the Malignancy of Cervical Cancer by Sponging MicroRNA-760 and Upregulating Hepatoma-Derived Growth Factor ([Dou et al 2020] ). ![] ,