LINC00504 Promotes the Malignant Biological Behavior of Breast Cancer Cells by Upregulating HMGB3 via Decoying MicroRNA-876-3p
Authors: Hongyu Wang
Can Wang
Yang Zhang
Zhuo Wang
Hao Yu
Liqian Dong
Huizheng Bao
Hong Xia
Journal: Cancer Management and Research (2021)
Discipline: CLINICAL MEDICINE
Keywords: ceRNA; high mobility group box 3; long intergenic non-protein coding RNA 504; therapeutic target.
Affiliations: Department of Hematology, Jilin Cancer Hospital, Changchun, Jilin, 130012, People's Republic of China., Department of Nephrology, Jilin Province FAW General Hospital, Changchun, Jilin, 130013, People's Republic of China., Department of Medical Oncology, Jilin Cancer Hospital, Changchun, Jilin, 130012, People's Republic of China.

Abstract:  Purpose: Long intergenic non-protein coding RNA 504 (LINC00504) is a long non-coding RNA that has an important regulatory role in a variety of human cancers. In this study, LINC00504 expression in breast cancer tissues and cell lines was detected. Studies were also conducted to determine the impact of LINC00504 on the tumor behavior of breast cancer cells. The potential mechanisms underlying the oncogenic role of LINC00504 in breast cancer cells were elucidated in detail. Methods: Expression of LINC00504 in breast cancer was analyzed by quantitative real-time polymerase chain reaction. The effects of LINC00504 on proliferation, apoptosis, in vitro migration and invasion, and in vivo tumor growth were elucidated using Cell Counting Kit-8 assay, flow cytometry, Transwell assays, and tumor xenograft models, respectively. Bioinformatics analyses in conjunction with RNA immunoprecipitation, luciferase reporter assays, and rescue experiments were conducted to investigate the underlying molecular mechanisms. Results: LINC00504 was upregulated in breast cancer tissues and cell lines. Knocking down LINC00504 suppressed breast cancer cell proliferation, migration, and invasion and facilitated apoptosis in vitro. In addition, tumor growth in vivo was significantly inhibited by LINC00504 depletion. Regarding the underlying mechanism, LIN00504 could function as a competing endogenous RNA in breast cancer by sponging microRNA-876-3p (miR-876-3p), resulting in the upregulation of high mobility group box 3 (HMGB3). Rescue experiments further revealed that miR-876-3p downregulation or HMGB3 upregulation effectively reversed the inhibitory effects of LIN00504 deficiency on breast cancer cells. Conclusion: The LIN00504-miR-876-3p-HMGB3 axis shows carcinogenic effects in modulating the biological behavior of breast cancer cells. This pathway may represent an effective target for CRC diagnosis and anticancer therapy. 

Retracted: No

PubPeer comments:
 Continuing a series on  much-travelled rulers used for scale in photographs of xenograft tumors . Fig 8B from [Yun et al (2021)] .  Representative images of tumor xenografts obtained from the sh-CERS6-AS1 and sh-NC groups . ![file] Fig 6B from [Li et al (2020)] .  Images of tumors . ![file] **Fig 6A from [Yu et al (2021)] **.  Representative photographs of tumor xenografts obtained from the shLINC00504 and sh-NC groups . ![file] All three images are notable for the distinctive damage at 9-cm. The three research teams are at Jilin University, though at different departments, with no authors in common. Were they passing the ruler around? ![file] The same design of ruler features in two other papers published at the same time, but do not show the damaged section, so perhaps they are different examples. *[left]* Fig 7A from [Cheng et al (2021)] .  Representative images of tumor xenografts harvested from the sh-UBA6-AS1 and sh-NC groups . *[right]* Fig 7A from [Chen, Gao Zhu (2021)] .  Images of excised tumour xenografts . ![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. ,