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Bohan Li,1 Jie Zhao,2 Qian Zhao,3 Dongjin Wu,2 Cheng Zhang,2 Kun Zhao,2 Yang Song,2 Chunzheng Gao2 1Health Management Center, The Second Hospital of Shandong University, Shandong 250033, People’s Republic of China; 2Department of Spine Surgery, The Second Hospital of Shandong University, Shandong 250033, People’s Republic of China; 3Jinan Central Hospital, The Affiliated Hospital of Shandong University, Shandong 250013, People’s Republic of ChinaCorrespondence: Dongjin WuDepartment of Spine Surgery, The Second Hospital of Shandong University, Shandong 250033, People’s Republic of ChinaEmail wuwudj2143@163.comPurpose: Dysregulation of microRNA-618 (miR-618) has been observed in multiple types of human cancer. However, whether miR-618 is implicated in osteosarcoma (OS) initiation and progression is still unclear. Hence, we measured the expression of miR-618 in OS tissues and cell lines. In addition, the roles of miR-618 and the mechanisms underlying its activities in OS cells were examined.Methods: The expression status of miR-618 in OS was analyzed by reverse-transcription quantitative PCR. The regulatory roles of miR-618 overexpression in OS were explored by the Cell Counting Kit-8 assay, flow-cytometric analysis, Transwell cell migration and invasion assays, and a tumor xenograft experiment.Results: The results revealed that the expression of miR-618 was notably lower in OS tissues and cell lines, and that the low miR-618 expression significantly correlated with the clinical stage and distant metastasis among patients with OS. Exogenous miR-618 expression significantly suppressed OS cell proliferation, migration, and invasion and induced apoptosis in vitro as well as slowed tumor growth in vivo. Mechanism investigation indicated that metadherin (MTDH) is a direct target gene of miR-618 in OS cells. A knockdown of MTDH mimicked the tumor-suppressive effects of miR-618 upregulation on OS cells. Notably, resumption of MTDH expression attenuated the miR-618–mediated reduction in OS cell growth and metastasis in vitro. In addition, miR-618 overexpression reduced the PTEN–AKT pathway output in OS cells both in vitro and in vivo through downregulation of MTDH.Conclusion: To the best of our knowledge, this is the first study to show that miR-618 exerts crucial tumor-suppressive actions in OS pathogenesis by directly targeting MTDH mRNA and reducing PTEN–AKT pathway output. These results will help to elucidate the functions of miR-618 in OS and suggest that this miRNA may be investigated as a therapeutic target in this disease.Keywords: microRNA-618, osteosarcoma, metadherin, proliferation, invasion

Li B, Zhao J, Zhao Q, et al. Onco Targets Ther. 2019;12:9795–9807. The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised over alleged image duplication in Figures 2C, 4C and 5C with similar images from unrelated articles, specifically: Figure 2C, panel U2OS miR-NC appears to have been duplicated with a similar image in Figure 2C from Li et al, 2019 (https://doi.org/10.18632/aging.102280). Figure 2C, panel U2OS miR-618 mimics appears to have been duplicated with a similar image from Figure 5c from Wu et al, 2020 (https://doi.org/10.1080/15384101.2020.1728024). Figure 4C, panel HOS si-MTDH appears to be have been duplicated with a similar image in Figure 4b from Zhao et al, 2020 (https://doi.org/10.1080/15384101.2020.1749404). Figure 5C, panel HOS miR-618 mimics+pCMV appears to have been duplicated with a similar image in Figure 2C from Li et al, 2019 (https://doi.org/10.18632/aging.102563) and Figure 5D from Chen et al, 2019 (https://doi.org/10.3892/ijmm.2019.4429). 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 “Retracted”. This retraction relates to this paper

OBJECTIVE: MicroRNAs (miRNAs) were popularly investigated in many cancers. The aim of this study was to evaluate the expression, role, and mechanism of microRNA-618 (miR-618) in human thyroid cancer (TC) cells. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction was carried out to examine the expression level of miR-618 in 20 TC tissues with 15 adjacent normal tissues. Synthesized mimics medicated miR-618 overexpression model was done in TC TPC-1 cell line. The effects of cell growth were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide method. In addition, PI staining followed by flow cytometry was performed to analyze cell cycle. Then, we performed Western blotting to analyze the impact of miR-618 overexpression on the classical PI3K/Akt signaling pathway. RESULTS: We confirmed previous findings that miR-618 was downregulated in TC. Functionally, we found that forced expression of miR-618 suppressed cell proliferation and led to G2/M arrest in TPC-1 cells. Mechanically, we showed that miR-618 overexpression induced a significant inhibition of PI3K/Akt signaling pathway in TPC-1 cells. Importantly, restoration of Akt reversed the growth inhibitory effects of miR-618. CONCLUSION: Taken together, our results described a growth-suppressive role of miR-618 in TC cells partially targeting the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]