<p>Long Non-Coding RNA DARS-AS1 Contributes to Prostate Cancer Progression Through Regulating the MicroRNA-628-5p/MTDH Axis</p>
Authors: Haitao Fan
Jia Cui
Junhui Hou
Siqing Liu
Zuomin Xiao
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: DARS antisense RNA 1; ceRNA theory; non-coding RNA; target therapy.
Affiliations: Department of Urology, The Second Hospital of Jilin University, Changchun, Jilin 130041, People's Republic of China., Department of Oncology & Radiotherapy, Qingdao Central Medical Group, Qingdao, Shandong 266000, People's Republic of China., Department of Outpatient, Qingdao Special Service Sanatorium of PLA Navy, Qingdao, Shandong 266071, People's Republic of China., Department of Clinical Laboratory, Jinan Jigang Hospital, Jinan, Shandong 250101, People's Republic of China., Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116023, People's Republic of China.

Abstract:  Purpose: DARS antisense RNA 1 (DARS-AS1) is a long non-coding RNA that has been validated as a critical regulator in several human cancer types. Our study aimed to determine the expression profile of DARS-AS1 in prostate cancer (PCa) tissues and cell lines. Functional experiments were conducted to explore the detailed roles of DARS-AS1 in regulating PCa carcinogenesis. Furthermore, the detailed mechanisms by which DARS-AS1 regulates the oncogenicity of PCa cells were uncovered. Methods: Reverse transcription quantitative polymerase chain reaction was performed to analyze DARS-AS1 expression in PCa tissues and cell lines. Cell Counting Kit-8 assays, flow cytometry analyses, Transwell assays, and tumor xenograft experiments were conducted to determine the regulatory effects of DARS-AS1 knockdown on the malignant phenotype of PCa cells. Bioinformatics analysis was performed to identify putative microRNAs (miRNAs) targeting DARS-AS1, and the direct interaction between DARS-AS1 and miR-628-5p was verified using RNA immunoprecipitation and luciferase reporter assays. Results: DARS-AS1 was highly expressed in PCa tissues and cell lines. In vitro functional experiments demonstrated that DARS-AS1 depletion suppressed PCa cell proliferation, promoted cell apoptosis, and restricted cell migration and invasion. In vivo studies revealed that the downregulation of DARS-AS1 inhibited PCa tumor growth in nude mice. Mechanistic investigation verified that DARS-AS1 functioned as an endogenous miR-628-5p sponge in PCa cells and consequently promoted the expression of metadherin (MTDH). Furthermore, the involvement of miR-628-5p/MTDH axis in DARS-AS1-mediated regulatory actions in PCa cells was verified using rescue experiments. Conclusion: DARS-AS1 functioned as a competing endogenous RNA in PCa by adsorbing miR-628-5p and thereby increasing the expression of MTDH, resulting in enhanced PCa progression. The identification of a novel DARS-AS1/miR-628-5p/MTDH regulatory network in PCa cells may offer a new theoretical basis for the development of promising therapeutic targets. 

Retracted: No

PubPeer comments:
 Two pairs of flow-cytometry plots seem to share most of their points in common, suggesting that both pairs are derived from single data sets. I have adjusted contrast and aspect ratios to facilitate comparison. ![file] ![file] Both right-hand panels are from Figs 1H, 2H, 4C, 5C. Both left-hand panels are from Figs 1f, 3c, 5c, 6c of [He et al (2020)] . ![file] -------------------------------------- ![] , 
 #1 ![file] For these two pictures, we can first see that there is a significant difference in cell density. The number of cells in our picture is significantly less than the apoptosis picture on the left. Secondly, in the parts circled in different colors in the figure, it can be seen that the scatter distribution of the two is completely different.! In these two apoptosis graphs, we use different colors to circle the difference in the scatter distribution between the two. At the same time, the naked eye can also see that the amount of cells we detect apoptosis is relatively small. ![file] For the similar shape of apoptosis, we think there may be the following reasons: 1) They are all tumor cells studied, and the tumor cells are similar in size, shape and habits; 2) These tumor cells are all transfected with Lipofectamine 2000u2122 liposomes. Acid, trypsin digestion after transfection, and centrifugation to collect cells, and all cells are processed by Annexin-V-Fluorescein Isothiocyanate (FITC) Apoptosis Kit; 3) Cell Quest acquisition software is the mainstream software for processing apoptosis. These factors may all lead to similar shapes of apoptosis pictures. , 
 #2 That s not how this works. In any case, it seems that at least one image in this paper overlaps with an image in another Dove Press paper. Careful readers will notice that the field of view is different in each paper, suggesting that the two figures were prepared by the same person who had access to a larger original. There is an overlap of author affiliations between the two papers, but I did not see an overlap among the authors. All this suggests a third-party may have contributed material for both papers. Figure 6D OncoTargets and Therapy (2020) doi: 10.2147 ott.s278582 https: pubpeer.com publications 0FA6780247E4D254B36177D09C2C03#4 Figure 5D Cancer Management and Research (2020) doi: 10.2147 cmar.s271021 https: pubpeer.com publications 6151F1D7C9E66F6611DFDE78C99763 *** ![file] , 
 Retracted [4 August 2022] . ---------------------- The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised regarding the integrity of the flow cytometry data shown in the article. In addition, there were also concerns regarding the duplication of images in Figure 5D with those from Figure 6D in Luo et al (2020) . Specifically, - Figure 5D, PC-3, #1, appears to have been duplicated with a similar image in Figure 6D, SW480, left hand panel, from Luo et al (2020). The authors did not respond to our queries and the decision was made to retract the article and the authors were notified of this. 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. , 
 - *[above]* Fig 1G from  Long noncoding RNA LINC00205 enhances the malignant characteristics of retinoblastoma by acting as a molecular sponge of microRNA-665 and consequently increasing HMGB1 expression ([Zhang et al 2020] ). - *[below]* **Fig 2I**. ![file] ------------------- - *[left]* Fig 3D from  Long Noncoding RNA LINC00525 Promotes the Aggressive Phenotype of Chordoma Through Acting as a microRNA-505-3p Sponge and Consequently Raising HMGB1 Expression ([Li et al 2020] ). - *[right]* **Fig 4E**. ![file] ,