<p>MicroRNA-652 suppresses malignant phenotypes in glioblastoma multiforme via FOXK1-mediated AKT/mTOR signaling pathway</p>
Authors: Yilei Wu
Chengxia Liu
Zhenzhen Song
Huimei Yang
Xia Wu
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: Forkhead-box K1; glioblastoma multiforme; malignant development; microRNA.
Affiliations: Department of Laboratory, The Third People's Hospital of Linyi, Linyi, Shandong 276023, People's Republic of China., Department of Oncology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, People's Republic of China., Department of Pathology, Linyi Cancer Hospital, Linyi, Shandong 276023, People's Republic of China.

Abstract:  Purpose: An increasing number of studies have documented that dysregulation of microRNAs (miRNAs) is common in glioblastoma multiforme (GBM). miR-652 is aberrantly expressed in various human cancers and plays important roles in numerous cancer-related processes. However, the expression profiles and potential roles of miR-652 in GBM remain largely unknown. Patients and methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine miR-652 expression in GBM tissues and cell lines. The effects of miR-652 upregulation on GBM cell proliferation, clone formation, apoptosis, migration and invasion were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, clone formation, flow cytometry and Transwell® migration and invasion assays, respectively. In vivo xenotransplantation was utilized to determine the effect of miR-652 on GBM tumor growth in vivo. Of note, the molecular mechanisms underlying the tumor-suppressing activity of miR-652 upregulation in GBM cells were also investigated using a series of experiments, including bioinformatics analysis, luciferase reporter assay, RT-qPCR and Western blot analysis. Results: miR-652 expression was considerably downregulated in GBM tissues and cell lines. Low miR-652 expression was strongly correlated with Karnofsky performance score and tumor size. Overall survival duration was shorter in GBM patients with low miR-652 expression than in those with high miR-652 expression. miR-652 resumption considerably suppressed the proliferation, clone formation, migration, and invasion and promoted the apoptosis of GBM cells in vitro. In addition, forkhead-box k1 (FOXK1) was demonstrated as the direct target gene of miR-652 in GBM cells. FOXK1 downregulation led to a tumor-suppressing activity similar to that of miR-652 upregulation. Restoration of FOXK1 expression partially neutralized the influence of miR-652 overexpression on GBM cells. Furthermore, ectopic miR-652 expression deactivated the AKT/mTOR pathway in GBM cells via FOXK1 regulation. Moreover, miR-652 impaired GBM tumor growth in vivo, probably caused by miR-652-mediated suppression of FOXK1/AKT/mTOR signaling. Conclusion: miR-652 inhibits FOXK1 and deactivates the AKT/mTOR pathway, thereby resulting in the suppression of malignant phenotypes of GBM cells in vitro and in vivo. 

Retracted: Yes

PubPeer comments:
 Figs 2D, 4D, 5D. ![file] The blue-boxed panel also appears in Figs 2C, 5C, 6C of [Cheng et al (2020)] . ![file] Here in context: ![file] There may be other panel matches, with other papers from this oeuvre. , 
 Please admire this montage of xenograft tumor images. Green, red, orange, blue boxes mark various pairs that appear to be the same tumors, rotated slightly and viewed from different angles. ![file] Upper row: - Fig 8A from [Dou et al (2020)] . A representative image of tumor xenografts from groups u201csi-FOXD2-AS1u201d and u201csi-NC.u201d Rotated through 90 deg to facilitate comparison. - Fig 8B from [Wang et al (2019)] .  Representative images of tumor xenografts excised from nude mice obtained 4 weeks after subcutaneous injection of Y79 cells transfected with miR-665 mimics or miR-NC. - Fig 7B from [Jiao, Liu Tian (2019)] .  Photograph of tumor xenograft derived from the nude mice injected with miR-493 mimics or miR-NC-transfected Tca8113 cells. Lower row: - Fig 7A from [Ren et al (2019)] .  Representative images of the [HOS] tumor xenografts in miR-758 mimics and miR-NC groups. - Fig 6A from [Zhou Li (2019)] .  Photographs of tumor xenografts were obtained from nude mice that were injected with miR-605 mimics or miR-NC transfected H460 cells . Rotated through 90 deg. - **Fig 8B from [Yang et al (2019)] **.  Photographs of [U251] tumor xenografts from the agomiR-652 and agomiR-NC groups. Rotated through 90 deg. , 
 Retracted [28 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 2D and 8B with similar images from unrelated articles, specifically: - Figure 2D, panel T98 agomiR-652 appears to have been duplicated with a similar image in Figure 6C from Cheng et al, . - Figure 8B appears to have been duplicated with similar images in Figure 7A from Ren et al, 2019 (http: www.ajcr.us files ajcr0088433.pdf). 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. , 
 - *[left]* Fig 4E from  Long Noncoding RNA ST7-AS1 Upregulates TRPM7 Expression by Sponging microRNA-543 to Promote Cervical Cancer Progression ([Qi et al 2020] ). - *[left]* **Fig 4E**. ![file] , 
 - Fig 3e from  LncRNA XIST upregulates TRIM25 via negatively regulating miR-192 in hepatitis B virus-related hepatocellular carcinoma ([Wang et al 2021] ; - **Fig 5C**; - Fig 2c from  MiR-182 regulates cell proliferation and apoptosis in laryngeal squamous cell carcinoma by targeting the CRR9 ([Lv et al 2019] ); - Fig 4b from  NEAT1 miR-23a-3p KLF3: a novel regulatory axis in melanoma cancer progression ([Ding et al 2019] ). ![file] , 
 - *[above]* Fig 2d from  SNHG17 enhances the malignant characteristics of tongue squamous cell carcinoma by acting as a competing endogenous RNA on microRNA-876 and thereby increasing specificity protein 1 expression ([Liu et al 2020] ). - *[below]* **Fig 6B**. ![file] , 
 - *[left]* Fig 2F. - *[right]* Fig 6E from  Long Noncoding RNA LINC00173 Promotes the Malignancy of Melanoma by Promoting the Expression of IRS4 Through Competitive Binding to microRNA-493 ([Fan et al 2020] ). ![file] Both papers are retracted, but it is still useful to document the extent of figure recycling within the oeuvre of this papermill. , 
 - *[above]* Fig 6A. - *[below]* Fig 4D from  MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy ([Li et al 2019] ). ![file] , 
 - *[left]* Fig 2c from  MicroRNA-939 Directly Targets em HDGF em to Inhibit the Aggressiveness of Prostate Cancer via Deactivation of the WNT u03b2-Catenin Pathway ([Situ et al 2020] ). - *[right]* **Fig 4C**. ![file] Both papers are retracted, but it is still worth documenting the extent of image recycling within this papermill s oeuvre. , 
 - *[left]* Fig 3C from  LncRNA HOTTIP leads to osteoarthritis progression via regulating miR-663a Fyn-related kinase axis ([He et al 2021] ) . - *[right]* **Fig 2C**. ![file] Not to forget this match: Fig 2C again, this time with *[left]* Fig 2b from  The microRNA-130a-5p RUNX2 STK32A network modulates tumor invasive and metastatic potential in non-small cell lung cancer ([Ma et al 2020] ). ![] ,