<p>Long Noncoding RNA PRR34-AS1 Aggravates the Progression of Hepatocellular Carcinoma by Adsorbing microRNA-498 and Thereby Upregulating FOXO3</p>
Authors: Shuangyu Qi
Zhaoming Liu
Hao Yao
Zhen Li
Jianxiong Tai
Binghui Xu
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: PRR34 antisense RNA 1; ceRNA regulation model; forkhead box O3; polymerase chain reaction.
Affiliations: Department of Hepatobiliary Surgery, Harrison International Peace Hospital, Hengshui, Hebei 053000, People's Republic of China., Department of Interventional Therapy, Harrison International Peace Hospital, Hengshui, Hebei 053000, People's Republic of China.

Abstract:  Purpose: Long noncoding RNAs are differentially expressed in hepatocellular carcinoma (HCC) and have been validated as essential regulators in HCC. However, there is limited knowledge regarding the detailed roles and mechanisms of most lncRNAs in HCC cells. In this study, the expression profiles of PRR34 antisense RNA 1 (PRR34-AS1) in HCC tissues and cell lines were determined. In addition, the detailed roles and underlying mechanisms of PRR34-AS1 in HCC cells were comprehensively elucidated. Methods: Reverse transcription-quantitative polymerase chain reaction (PCR) was performed to measure PRR34-AS1 expression in HCC cells. Cell proliferation, apoptosis, and migration and invasion were evaluated in vitro using the cell counting kit-8 (CCK-8) assay, flow cytometric analysis, and transwell cell migration and invasion assays, respectively. In vivo tumor growth was determined using tumor xenograft experiments. The potential miRNA targets of PRR34-AS1 were predicted via bioinformatic analysis and further confirmed using the luciferase reporter assay, RNA immunoprecipitation assay, and reverse transcription-quantitative PCR. Results: PRR34-AS1 was highly expressed in HCC tissues and cell lines, and its interference suppressed HCC cell proliferation, migration, and invasion but promoted cell apoptosis in vitro. In addition, loss of PRR34-AS1 decreased tumor growth in HCC cells in vivo. Mechanistically, PRR34-AS1 functions as a miR-498 sponge and subsequently increases forkhead box O3 (FOXO3) expression in HCC cells. Rescue experiments revealed that the suppressive effects triggered by PRR34-AS1 knockdown on the malignant characteristics of HCC cells could be abrogated by inhibiting miR-498 or restoring FOXO3 expression. Conclusion: The depletion of PRR34-AS1 suppresses the oncogenicity of HCC cells by targeting the miR-498/FOXO3 axis. Therefore, the PRR34-AS1/miR-498/FOXO3 pathway may offer a basis for HCC treatment. 

Retracted: No

PubPeer comments:
 Here are multiple appearances of what seems to be the same well-traveled ruler, marked by a distinctive scratch just to the right of 2 .Different teams of researchers from six different institutions somehow used it to provide scale for the xenograft tumors in their studies. There would be no problem if all the images had been recorded at a single lab, but the papers do not mention outsourcing any of the experiments to an outside contractor. Upper row: - Fig 7B from [Chen et al (2021)] .  Representative images of subcutaneous tumours collected from the sh-USP30-AS1 and sh-NC groups. Rotated through 90 deg for ease of comparison. - Fig 8A from [Luo et al (2020)] .  Representative images of tumor xenografts originating from SW480 cells stably expressing sh-LINC00239 or sh-NC. Rotated through 90 deg. - Fig 7A from [Liu et al (2020)] .  Representative images of tumor xenografts that originated from SW480 cells stably overexpressing sh-VPS9D1-AS1 or sh-NC . ![file] Middle row: - Fig 7B from [He et al (2021)] .  At 31 days following cell injection, all mice were euthanized and tumor xenografts were resected and imaged . - **Fig 6B from [Liu et al (2020)] **.  All mice were euthanized at the end of the experiment, and the tumor xenografts were harvested and imaged . Rotated through 90 deg. - Fig 8A from [Yang, Yang Wang (2020)] .  Tumor growth curves were plotted according to the tumor volumes measured weekly . ![file] Lower row: - Fig 7B from [Li et al (2020)] .  Representative images of tumor xenografts collected from short hairpin RNA (sh)-LINC00525 and control (sh-NC) groups . - Fig 6A from [Dai et al (2020)] .  After 28 days post-inoculation, mice were euthanized and tumor xenografts were dissected and photographed . ![file] , 
 The travelling ruler is not the only source of concern - just the easiest to present. Another source is the implausible WBs in this paper, resembling strings of sausages, and also found in a distinct *oeuvre*. https: docs.google.com spreadsheets d 1X401JM6CcpTSkbKsPsOl20pRKQ-ns1S_J5pTwtBjqPw edit?usp=sharing For now, here are the paper s flow-cytometry scatterplots: Figs 1H ( flow cytometric analysis were used to detect the proliferation and apoptosis of HuH7 and SNU-182 cells after PRR34-AS1 depletion ), 3C ( apoptosis of miR-498-overexpressed HuH7 and SNU-182 cells were analyzed via ... flow cytometric analysis ), 5C, 5H. ![file] Compare, for instance, Figs 2C, 4B, 5C, 6E from [Wu et al (2019)] : ![] And Figs 2C, 4D, 5C of [Sun et al (2020)] . ![] I have not checked for pairs of panels that match exactly, but the similarity is at least at the level of experimental replications. , 
 Expression of Concern, [15 October 2021] . ---------------------- The Editor and Publisher of *Cancer Management and Research* wish to publish an Expression of Concern for the published article. Following publication, concerns were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. The authors provided several files in response to our queries but they did not satisfy our requirements to confirm the authenticity of some types of data. In addition, there were unexplained similarities between some of the figures presented in this article, and figures presented in articles by different authors groups. As yet, the authors have not provided a satisfactory explanation for this. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. , 
 Will it help the investigation if I point out some overlaps with other papers by unrelated authors? Here, comparing Fig 5E *[right]* with *[left]* 5E from  Long noncoding RNA VPS9D1-AS1 augments the malignant phenotype of non-small cell lung cancer by sponging microRNA-532-3p and thereby enhancing HMGA2 expression ([Han et al 2020] ) **[undergoing investigation]** ![file] , 
 Retracted [21 June 2022] . -------------------------- At the authors request, the Editor and Publisher of Cancer Management and Research wish to retract the published article. Following publication of the Expression of Concern for this article the authors contacted the journal and explained they were unable to provide adequate original data for their study. In addition, concerns were also raised regarding the alleged duplication of images in Figure 5E with those from another article. Specifically, - Figure 5E, SNU-182, si-PRR34-AS1+miR-498 inhibitor appears to have been duplicated with an image from Figure 4E, H460, agomir-NC from Han et al, 2020 . The authors were unable to provide an explanation for the duplicated images. 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. ,