<p>Long Noncoding RNA VPS9D1-AS1 Sequesters microRNA-525-5p to Promote the Oncogenicity of Colorectal Cancer Cells by Upregulating HMGA1</p>
Authors: Bing Wang
Yuehan Ma
Guodong Liang
Yubo Yang
Xianmei Jin
Xueying Zhang
Hairui Liu
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: VPS9D1 antisense RNA 1; colorectal cancer; competing endogenous RNA model; therapeutic target.
Affiliations: Department of Abdominal Surgery, Jilin Cancer Hospital, Changchun, Jilin 130021, People's Republic of China., Department of Oncology Medicine, Jilin Cancer Hospital, Changchun, Jilin 130021, People's Republic of China., Department of Childhood Solid Tumor, First Hospital of Jilin University, Changchun, Jilin 130021, People's Republic of China., Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130021, People's Republic of China.

Abstract:  Background: The long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) has emerged as a critical regulator in non-small-cell lung, gastric, and prostate cancers. In this study, we measured the expression levels of VPS9D1-AS1 in colorectal cancer (CRC) and determined the role of VPS9D1-AS1 in regulating the biological activities of CRC cells. In addition, we thoroughly elucidated the molecular mechanism mediating the oncogenic activities of VPS9D1-AS1 in CRC. Methods: The expression levels of VPS9D1-AS1 in CRC tissues and cell lines were detected via quantitative reverse transcription-polymerase chain reaction. Loss-of-function experiments were performed to detect the effects of VPS9D1-AS1 silencing on CRC cell proliferation, apoptosis, migration, and invasion as well as on tumor growth in vivo. Bioinformatics analysis predicted the potential microRNAs (miRNAs) interacting with VPS9D1-AS1, and this prediction was further confirmed via RNA immunoprecipitation and luciferase reporter assays. Results: Our results demonstrated the upregulated expression of VPS9D1-AS1 in CRC tissues and cell lines. Functionally, VPS9D1-AS1 interference suppressed CRC cell proliferation, migration, and invasion and promoted cell apoptosis in vitro. In addition, the loss of VPS9D1-AS1 hindered tumor growth in vivo. Mechanistic studies identified VPS9D1-AS1 as a competing endogenous RNA in CRC cells, in which VPS9D1-AS1 acted as a molecular sponge of miR-525-5p and consequently increased the expression of high-mobility group AT-hook 1 (HMGA1). Moreover, rescue experiments revealed that the regulatory effects of VPS9D1-AS1 deficiency on CRC cells were abolished after miR-525-5p inhibition or HMGA1 restoration. Conclusion: The newly identified competing endogenous RNA pathway involving VPS9D1-AS1, miR-525-5p, and HMGA1 is implicated in the control of CRC progression and may provide an effective target for CRC diagnosis and therapy. 

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] , 
 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. ,