<p>MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/&beta;-catenin pathway</p>
Authors: Fengyan Zhang
Yong Lv
Shuai Wang
Wenzhan Wang
Shanshan Du
Journal: Cancer Management and Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: Wnt/Œ≤-catenin pathway; high-mobility group box 1; microRNA-665; oncogenicity; retinoblastoma.
Affiliations: Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People's Republic of China.

Abstract:  Purpose: Previous studies have revealed that microRNA-665 (miR-665) is dysregulated in a variety of human cancers. However, little is known regarding its expression profiles and functions in retinoblastoma (RB). Therefore, the aims of our study were to evaluate miR-665 expression in RB and determine the precise roles of miR-665 in the progression of RB. Patients and methods: Herein, RT-qPCR was used to determine miR-665 expression levels in RB tissues and cell lines, and a series of functional experiments were performed to explore the influence of miR-665 on RB cell proliferation, colony formation, apoptosis, migration, and invasion as well as tumor growth. The molecular mechanisms underlying the tumor-suppressive action of miR-665 in RB were also explored. Results: We found that miR-665 was markedly reduced in RB tissues and cell lines and that lower miR-665 expression was strongly associated with tumor size, TNM stage, and differentiation in patients with RB. Exogenous expression of miR-665 suppressed cell proliferation, colony formation, migration, and invasion, and induced cell apoptosis in RB cells, while silencing miR-665 expression had the opposite effects. In addition, upregulation of miR-665 decreased the tumor growth of RB cells in vivo. High-mobility group box 1 (HMGB1) was identified as a direct target of miR-665 in RB cells, and decreasing the expression of HMGB1 simulated the regulatory effects of miR-665 overexpression in RB cells, while knockdown of HMGB1 expression counteracted the miR-665-mediated antitumor effects in RB cells. Moreover, miR-665 was shown to regulate the Wnt/Œ≤-catenin signaling pathway by targeting HMGB1 in vitro and in vivo. Conclusion: Taken together, our in vitro and in vivo results suggest that miR-665 acts as a tumor-suppressive miRNA in RB by directly targeting HMGB1 and inactivating the Wnt/Œ≤-catenin pathway. Hence, this miRNA is a candidate prognostic biomarker and therapeutic target in patients with RB. 

Retracted: Yes

PubPeer comments:
 Figs 2D, 4D, 5D.  Apoptosis was examined by flow cytometric analysis in Y79 cells transfected with miR-665 mimics and WERI-RB-1 cells transfected with a miR-665 inhibitor ;  Flow cytometric analysis was applied to detect apoptosis in HMGB1-silenced Y79 and WERI-RB-1 cell ;  ... apoptosis were examined by using ... flow cytometric analysis .  Blue box marks a panel that also appears in Figs 2C, 5C, 6C of [Cheng et al (2020)] .   I did not search for further matches with other panels or with other papers in this oeuvre. https: docs.google.com spreadsheets d 1X401JM6CcpTSkbKsPsOl20pRKQ-ns1S_J5pTwtBjqPw edit?usp=sharing , 
 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.  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 [18 September 2021] . --------------------- The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised over alleged image duplication in Figures 4D and 8B with similar images from unrelated articles, specifically: - Figure 4D, panel WERI-RB-1 si-HMGB1 appears to have been duplicated with a similar image in Figure 2C from Cheng et al, 2020 . - Figure 8B, panels miR-NC; miR-665 mimics, far left and miR-NC; miR-665 mimics, centre-right appear to have been duplicated with similar images in Figure 8A from Dou et al, 2020 and Figure 7B from Jiao et al, 2019 , respectively. 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. ,