<p>microRNA-493 inhibits tongue squamous cell carcinoma oncogenicity via directly targeting HMGA2</p>
Authors: Zhen Tian
Yingying Liu
Dan Jiao
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: gene therapy; high-mobility group AT-hook 2; microRNA-493; tongue squamous cell carcinoma.
Affiliations: Department of Ultrasound, China-Japan Union Hospital, Jilin University, Changchun 130033, People's Republic of China., Department of Nephrology, China-Japan Union Hospital, Jilin University, Changchun 130033, People's Republic of China., Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun 130033, People's Republic of China.

Abstract:  Backgrounds: microRNA-493-3p (miR-493) has been reported to be critically downregulated in multiple types of human cancer. However, the expression level, biological roles and underlying mechanism of miR‑493 in tongue squamous cell carcinoma (TSCC) remain to be elucidated. Methods: RT-qPCR was utilized for the determination of miR-493 expression in TSCC tissues and cell lines. The influence of miR-493 overexpression on TSCC cell proliferation, apoptosis, migration, invasion in vitro and tumor growth in vivo were explored via MTT assay, flow cytometry analysis, cell migration and invasion assays, and xenograft tumors in nude mice, respectively. Bioinformatics analysis, luciferase reporter assays, RT-qPCR and Western blotting were performed to clarify the potential mechanisms involved in the action of miR-493 in TSCC cells. Results: miR-493 was significantly downregulated in TSCC tissues and cell lines. Decreased miR-493 expression was notably correlated with tumor differentiation, depth of invasion and TNM stage. Additionally, patients with TSCC having low miR-493 expression showed lower overall survival rate. Functionally, miR-493 upregulation inhibited TSCC cell proliferation, migration, invasion in vitro; induced cell apoptosis; and decreased the tumor growth in vivo. Bioinformatics analysis followed by luciferase reporter assays also demonstrated that miR-493 directly bound to the 3'-untranslated region of high-mobility group AT-hook 2 (HMGA2) in TSCC cells, and therefore reduced HMGA2 expression at the mRNA and protein level. Furthermore, HMGA2 was overexpressed in TSCC tissues and inversely correlated with miR-493. Moreover, silenced HMGA2 expression simulated the tumor-suppressing roles of miR-493 overexpression on TSCC cells. HMGA2 overexpression eliminated the inhibitory roles of miR-493 overexpression on TSCC cells. Conclusion: These observations demonstrated that miR-493 is a tumor suppressor inhibited the oncogenicity of TSCC cells by directly targeting HMGA2. These results provide sufficient evidence for the miR-493/HMGA2 axis as a novel therapeutic target for the treatment of patients with TSCC in the future. 

Retracted: Yes

PubPeer comments:
 IT appears that an image in figure 2 was used twice ![file] , 
 It is because of the mistake during the graphical plot. ![file] We attached the original figure of miR-493 mimic(CAL-27). I regret deeply this mistake. , 
 Just one more question; Figs 2C, 5C, 6C: ![file] Blue box marks a panel that also appears in [Zhang et al (2019)] . ![file] Here in context: ![file] How did this happen? Are there any other flow-cytometry scatterplots that appeared in previous papers, with different identifications? , 
 Fig 2C, 5C, 6C again. ![] A panel also appears in Figs 2C, 5C of [Wan et al (2019)] (with some points absent). ![] , 
 Figs 2D E, 5D E, 6D E. I have replaced one panel with the author s correction from comment #2. ![] Figs 2D E, 4E F, 5F G from [Zhao, Li Yu (2019)] . ![] Blue rectangles mark the same panel appearing in both papers. How to explain the duplication? , 
 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. , 
 #4 Fig 2C, 5C, 6C again, again. ![] One panel, marked with a green box, matches panels in Figs 2E, 5E of [Guo Xue (2020)] and in Figs 2B, 4D from [Liu et al (2019)] . ![] In context: ![] ![] , 
 Retracted [3 September 2021] . --------------------------------- The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised over alleged image duplication in Figure 2E between panels Tca8113 and CAL-27, miR-493 mimics. There were also concerns over the alleged duplication of images in Figures 6C and 6E and with similar images from unrelated studies, specifically: - Figure 6C, panel CAL-27, miR-NC appears to have been duplicated with a similar image in Figure 4D from Zhang et al, 2019 . - Figure 6E, panel CAL-27, miR-493 mimics+pcDNA3.1 appears to have been duplicated with a similar image in Figure 4E from Zhao et al, 2019 . The authors responded to our queries but were unable to provide an explanation for the alleged image duplication and could not provide the original raw data for their study and have therefore agreed to retract the article. 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. ,