<p>MicroRNA-936 targets FGF2 to inhibit epithelial ovarian cancer aggressiveness by deactivating the PI3K/Akt pathway</p>
Authors: Shanshan Wu
Ying Ni
Cuihong Li
Zixuan Pan
Shunrui Yu
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: PI3K/Akt pathway; epithelial ovarian cancer; fibroblast growth factor 2; microRNA-936.
Affiliations: Department of Gynecology and Obstetrics, Yidu Central Hospital of Weifang, Weifang 262500, People's Republic of China., Department of Emergency, Yidu Central Hospital of Weifang, Weifang 262500, People's Republic of China., Department of Oral, Weifang Nursing Vocational College, Weifang 262000, People's Republic of China., Department of Gynecology, The Affiliated Hospital of Weifang Medical University, Weifang 261031, People's Republic of China.

Abstract:  Purpose: MicroRNA-936 (miR-936) was previously reported to be dysregulated and involved in the development of non-small cell lung cancer and glioma. However, the functional roles of miR-936 in epithelial ovarian cancer (EOC) remain unclear. In this study, we aimed to evaluate miR-936 expression in EOC and investigate its regulatory role in EOC cell behavior. Methods: The expression of miR-936 in EOC was measured by RT-qPCR. Cell proliferation, apoptosis, migration, and invasion in vitro, as well as tumor growth in vivo, were determined by CCK-8, flow cytometry, migration and invasion assays, and xenograft models in nude mice, respectively. Bioinformatics analysis, luciferase reporter assays, RT-qPCR, and Western blot analysis were performed to investigate the relationship between miR-936 and fibroblast growth factor 2 (FGF2). Results: miR-936 expression was significantly downregulated in EOC tissues and cell lines. Low miR-936 expression was found to be correlated with the tumor size, FIGO stage, and lymphatic metastasis in EOC patients. Functional experiments indicated that ectopic miR-936 expression suppressed EOC cell proliferation, migration, and invasion; promoted cell apoptosis; and decreased tumor growth in vivo. In addition, the FGF2 gene was verified to be a direct target of miR-936 in EOC cells. FGF2 expression levels were upregulated in EOC tissues and were inversely correlated with miR-936 expression. Furthermore, effects of FGF2 silencing were similar to those of miR-936 overexpression in EOC cells. Recovered FGF2 expression rescued the miR-936-induced inhibitory effects in EOC cells. Notably, miR-936 was able to deactivate the PI3K/Akt signaling pathway in EOC cells by regulating FGF2 both in vitro and in vivo. Conclusion: Altogether, our findings provided initial evidence that miR-936 inhibits the aggressiveness of EOC cells in vitro and in vivo, at least partially, by targeting FGF2-mediated suppression of the PI3K/Akt pathway. Therefore, the miR-936/FGF2/PI3K/Akt pathway is a promising therapeutic target for the treatment of EOC patients. 

Retracted: Yes

PubPeer comments:
 Figs 2C, 4C, 5C. ![file] The pink-boxed panel appears in at least two other papers: Figs 2D, 5D, 6D of [Zhang et al (2018)] , and Fig 2D,5D,6D of [Wu et al (2018)] . ![file] Green-boxed panel is also shared with Wu et al (2018). ![file] Zhang et al for context: ![] Wu et al for context: ![file] Other matches may exist with other papers from this oeuvre. , 
 #1 Figs 2C, 4C, 5C again; now with a brown box, to match a panel from Figs 2C, 4C, 5C in [Yang et al (2019)] . ![] ![] , 
 *[left]* Fig 7A.  Representative images of tumor xenografts obtained from miR-936 mimics and miR-control groups . *[right]* Fig 8A from [Zhao et al (2018)] .  Representative images of the miR-511 mimics-transfected and miR-NC-transfected isolated xenograft tumors. Rotated through 90 deg for convenience. I have concerns. ![file] , 
 Retracted [4 October 2021] . ------------------------------ The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised over alleged image duplication in Figures 4C, 5C and 7A with similar images from unrelated articles, specifically: - Figure 4C, panel CAOV-3 si-NC appears to have been duplicated with a similar image in Figure 5C from Yang et al, 2019 . - Figure 4C, panel CAOV-3 si-FGF2 appears to have been duplicated with a similar image in Figure 5D from Wu et al, 2018 . - Figure 5C, panel SKOV3 miR-control appear to have been duplicated with a similar image in Figure 6D from Zhang et al, 2018 and Figure 5D from Wu et al, 2018 . - Figure 7A appears to have been duplicated with a similar image in Figure 8A from Zhao et al, 2018 . The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication and could not provide satisfactory original data for their study. The Editor 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. ,