miR-488 inhibits cell growth and metastasis in renal cell carcinoma by targeting HMGN5
Authors: Xiangbo Kong
Xin Wei
Lili Yu
Journal: OncoTargets and Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: HMGN5; metastasis; miRNA-488; proliferation; renal cell carcinoma.
Affiliations: Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, China.

Abstract:  Purpose: microRNAs are thought to play crucial roles in tumorigenesis. Dysregulation of miR-488 has been implicated to be involved in several cancer progressions. However, the biological functions of miR-488 in renal cell carcinoma (RCC) remain unclear. This study aimed to explore the molecular mechanism underlying the role of miR-488 in RCC development. Materials and methods: The expression levels of miR-488 were detected in 38 paired RCC tumor samples and cell lines by quantitative real-time polymerase chain reaction method. miR-488 was upregulated by mimics transfection in RCC cell lines. MTT, colony formation, transwell assay, flow cytometry assay, and a xenograft model were performed to determine cell proliferation, invasion, migration, epithelial-to-mesenchymal transition, and apoptosis in vitro and in vivo. Moreover, the potential target of miR-488 was verified by dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and Western blot. The correlation between miR-488 expression and its target gene expression was confirmed by Spearman's correlation analysis in 38 selected RCC tissue samples. Results: We found that miR-488 was remarkably downregulated in human RCC samples and cell lines compared with paired normal tissues and cell lines. Functional investigations revealed that overexpression of miR-488 significantly suppressed cell proliferation, invasion, and migration, and promoted cell apoptosis in RCC cells. Nucleosome binding protein 1 (high-mobility group nucleosome binding domain 5 [HMGN5]) was identified as a direct target of miR-488, and an inverse relationship was found between miR-488 expression and HMGN5 mRNA levels in RCC specimens. Rescue experiments suggested that restoration of HMGN5 partially abolished miR-488-mediated cell proliferation and invasion inhibition in RCC cells through regulating phosphatidylinositol 3-kinase/protein kinase B/the mammalian target of rapamycin and epithelial-to-mesenchymal transition signaling pathways. Conclusion: These data indicated that miR-488 acted as a tumor suppressor in RCC proliferation and invasion by targeting HMGN5, which might provide potential therapeutic biomarker for RCC patients. 

Retracted: Yes

PubPeer comments:
 Some panels in Figure 3 appears to look unexpectedly similar to each other, if some of them are rotated. Boxes of the same color highlight areas that look similar.  , 
 I encountered. this paper independently . As Dr Bik has observed, in Fig 3A (migration assay) the A498  miR-NC involves the same graphic elements as the 786-O version, but rotated through 90 deg., rescaled, and shifted slightly relative to one another. The ellipse marks a zone where the rearrangement of graphic elements is especially great.  Fig 3B, Again, echoing Dr Bik s observation that two  invasion panels involve the same graphic elements, albeit rotated through ~40 deg, rescaled, and rearranged.  , 
 Two other papers nominally written by Lili Yu (of Department of Radiology, China-Japan Union Hospital of Jilin University) show hallmarks indicating that their real source was a papermill. https: pubpeer.com publications 7F28FED7FFAEFAAF9310107096AD8A https: pubpeer.com publications CB6A6446B6ACE3A8CF4D3C95750AF8 , 
 #2 Echoing Dr Bik s comment on the miR-488 Migration panels. Yes, there is migration.  , 
 Retracted [4 May 2020] . -------------------------------- The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. It came to the journals attention that the article contained instances of alleged image manipulation. Specifically: Figure 3A panel 786-O miR-NC appears to be duplicated with panel A498 miR-NC which has been rotated clockwise by ~90u00b0. Figure 3B panel 786-O miR-NC appears to be duplicated with panel A498 miR-NC which has been rotated clockwise by ~45u00b0 and had some elements altered. Figure 3B panel 786-O miR-488 appears to be duplicated with panel A498 miR-488 which has been rotated clockwise by ~90u00b0. The western blots for Figure 5A panel 786-O HMGN5 appear to be duplicated with Figure 5F panel 786-O N-cadherin. The western blots for Figure 5A panel A498 HMGN5 appear to be duplicated with Figure 5F panel A498 N-cadherin. We tried to contact the authors but despite several attempts received no response. The Editor has determined the findings of the study are no longer valid and requested 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. ,