<p>Long Non-Coding RNA ASB16-AS1 Functions as a miR-760 Sponge to Facilitate the Malignant Phenotype of Osteosarcoma by Increasing HDGF Expression</p>
Authors: Fei Wang
Ruofeng Yin
Junzhi Liu
Dongxu Zhao
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: ASB16-AS1; hepatoma-derived growth factor; microRNA-760; osteosarcoma therapy.
Affiliations: Department of Orthopedics, China-Japan Union Hospital Jilin University, Changchun, Jilin 130033, People's Republic of China., Department of Quality Control, China-Japan Union Hospital Jilin University, Changchun, Jilin 130033, People's Republic of China.

Abstract:  Purpose: ASB16 antisense RNA 1 (ASB16-AS1) is a cancer-associated long non-coding RNA that contributes to tumorigenesis and tumor development. Nevertheless, to the best of our knowledge, whether and how ASB16-AS1 is implicated in osteosarcoma (OS) malignancy remains unclear and therefore warrants exploration. Our current study focused on making in-depth investigation of ASB16-AS1 in OS. In the present study, the expression pattern of ASB16-AS1 in OS tissues and cell lines was analyzed. In addition, we examined the clinical value of ASB16-AS1 for OS patients. Furthermore, we explored the impacts of ASB16-AS1 on the malignant phenotype of OS cells in vitro and in vivo as well as the underlying mechanism. Methods: ASB16-AS1, microRNA-760 (miR-760) and hepatoma-derived growth factor (HDGF) expressions were measured using reverse transcription-quantitative PCR. Cell proliferation and apoptosis were evaluated using CCK-8 and flow cytometry analyses, respectively, and cell migration and invasion were determined via cell migration and invasion assays. Results: ASB16-AS1 expression was significantly elevated in OS tissues and cell lines, and increased ASB16-AS1 expression was related to patients' tumor size, TNM stage, and distant metastasis. The overall survival rate of OS patients presenting high ASB16-AS1 expression was shorter than that of patients presenting low ASB16-AS1 expression. Reduced ASB16-AS1 expression inhibited OS cell proliferation, migration, and invasion; promoted cell apoptosis; and impaired tumor growth in vivo. Mechanistically, ASB16-AS1 served as a sponge for miR-760 and positively modulated the expression of its target HDGF. Finally, inhibiting miR-760 and restoring HDGF expression abolished the impacts of ASB16-AS1 knockdown on the malignant characteristics of OS cells. Conclusion: ASB16-AS1 is a novel oncogenic lncRNA in OS cells. ASB16-AS1 increased HDGF expression by sponging miR-760, thereby conferring cancer-promoting roles in OS. ASB16-AS1 is a potential early diagnostic and therapeutic target in OS. 

Retracted: Yes

PubPeer comments:
 Figs 2C, 4B, 6B.  Green and light green boxes mark two panels that also appeared in Figs 2C, 5C, 6C of [Cheng et al (2020)] .   Here in context:  There may be matches with other panels or with other papers from this oeuvre. https: docs.google.com spreadsheets d 1X401JM6CcpTSkbKsPsOl20pRKQ-ns1S_J5pTwtBjqPw edit#gid=0 , 
 Dear Hoya Camphorifolia Thanks a lot for pointing out our mistake. We will check the original data of cell apoptosis, and reply to you as soon as possible. Also, we will repeat this experiment and confirm the data. We are very sorry for our mistakes. Thanks again for your kind reminding. With kind personal regards. , 
  Right-hand panel is from Fig 6B. Left-hand panel is from Fig 5C of [Kang et al (2019)] . Central panel from Fig 3D of [Yu et al (2020)] . Here in context:  ---------------------------------  ----------------------------------------  , 
 Could the authors comment on the duplication of a flow-cytometry plot from Fig 2C of this paper with one from Figs 2d, 4d, 6c, 7d of [Ai et al (2020)] ?  Here in context:   There may be other duplications, or matches with other panels from this oeuvre. https: docs.google.com spreadsheets d 1X401JM6CcpTSkbKsPsOl20pRKQ-ns1S_J5pTwtBjqPw edit#gid=0 , 
 Retracted, [3 September 2021] . --------------------------- The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised regarding the alleged duplication of images in Figures 2C, 4B and 6B with similar images from unrelated articles, specifically: - Figure 2C, panel U2OS si-ASB16-AS1 appears to have been duplicated with a similar image in Figure 6C, panel Huh7 si-GAS6-AS+NC inhibitor from Ai et al, 2020 . - Figure 4B, panels HOS agomir-NC; agomir-760 appear to have been duplicated with similar images in Figure 6C, panel Sw1990 miR-769 mimics+pcDNA3.1-ETS1 and 5C, panel Panc-1 si-ETS1, respectively from Cheng et al, 2020 . - Figure 6B, panel U2OS si-NC appears to have been duplicated with similar images in Figures 5C, panel H522 NC siRNA from Kang et al, 2019 and 3D, panel si-HAND2-AS1 from Yu et al, 2020 , respectively. 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 or ethics approval documents 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. , 
 - *[left]* Fig 7A from  microRNA-944 inhibits the malignancy of hepatocellular carcinoma by directly targeting IGF-1R and deactivating the PI3K Akt signaling pathway ([Lv et al 2019] ). - *[right]* **Fig 6D**.  Both papers are retracted, but it is still worth documenting the level of image reuse in the oeuvre of this papermill. , 
 - *[above]* Fig 7E. - *[below]* Fig 6d e from  Long noncoding RNA RUSC1-AS1 promotes tumorigenesis in cervical cancer by acting as a competing endogenous RNA of microRNA-744 and consequently increasing Bcl-2 expression ([Guo et al 2020] ).  ,