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LINC00504 Promotes the Malignant Biological Behavior of Breast Cancer Cells by Upregulating HMGB3 via Decoying MicroRNA-876-3p

Authors Yu H, Dong L, Wang H, Zhang Y, Wang Z, Wang C, Xia H, Bao H

Received 9 August 2020

Accepted for publication 26 January 2021

Published 22 February 2021 Volume 2021:13 Pages 1803—1815

DOI https://doi.org/10.2147/CMAR.S276290

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Bilikere Dwarakanath


Hao Yu,1 Liqian Dong,2 Hongyu Wang,3 Yang Zhang,3 Zhuo Wang,3 Can Wang,3 Hong Xia,1 Huizheng Bao1

1Department of Hematology, Jilin Cancer Hospital, Changchun, Jilin, 130012, People’s Republic of China; 2Department of Nephrology, Jilin Province FAW General Hospital, Changchun, Jilin, 130013, People’s Republic of China; 3Department of Medical Oncology, Jilin Cancer Hospital, Changchun, Jilin, 130012, People’s Republic of China

Correspondence: Huizheng Bao
Department of Hematology, Jilin Cancer Hospital, 1018 Huguang Road, Changchun, Jilin, 130012, People’s Republic of China
Email hemat_baohuizheng@163.com

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.

Keywords: high mobility group box 3, long intergenic non-protein coding RNA 504, therapeutic target, ceRNA

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