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HMGB3 silence inhibits breast cancer cell proliferation and tumor growth by interacting with hypoxia-inducible factor 1α

Authors Gu J, Xu T, Huang QH, Zhang CM, Chen HY

Received 6 February 2019

Accepted for publication 10 April 2019

Published 31 May 2019 Volume 2019:11 Pages 5075—5089

DOI https://doi.org/10.2147/CMAR.S204357

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Justinn Cochran

Peer reviewer comments 4

Editor who approved publication: Dr Chien-Feng Li


Jun Gu, Tao Xu, Qin-Hua Huang, Chu-Miao Zhang, Hai-Yan Chen

Department of Health Check-Up Center, Jinshan Hospital, Fudan University, Shanghai 201508, People’s Republic of China

Background: Breast cancer is the most common malignant tumor that affects women with higher incidence. High-mobility group box 3 (HMGB3) plays critical functions in DNA repair, recombination, transcription and replication. This study aimed to investigate the effects of HMGB3 silence on mammosphere formation and tumor growth of breast cancer.
Methods: LV5-HMGB3 and LV3-siHMGB3 vectors were transfected into MCF10A, MDA-MB-231, HCC1937, ZR-75-1 and MCF7 cells. Cell counting kit-8 (CCK-8) assay was used to evaluate cell proliferation. Xenograft tumor mice model was established by injection of MDA-MB-231. qRT-PCR and western blot were used to examine the expression of Nanog, Sox2 and OCT-4. Mammosphere forming assay was employed to evaluate mammosphere formation both in vivo and in vitro. Dual luciferase assay was utilized to verify the interaction between HMGB3 and hypoxia-inducible factor 1α (HIF1α). CD44+,/CD24−, was assessed with flow cytometry.
Results: HMGB3 expression was higher significantly (p<0.05) in cancer cells compared to normal cells. HMGB3 overexpression significantly (p<0.05) enhanced and HMGB3 silence reduced cell proliferative mice compared to MCF10A and MDA-MB-231, respectively. HMGB3 overexpression enhanced and HMGB3 silence inhibited mammosphere formation. HMGB3 overexpression upregulated and HMGB3 silence downregulated Nanog, SOX2 and OCT-4 genes/proteins in MCF10A and MDA-MB-231 cells, respectively. HMGB3 silence reduced CD44+,/CD24−, levels in cancer cells. Silence of HMGB3 strengthened reductive effects of PTX on tumor sizes, iPSC biomarkers and mammosphere amounts in xenograft tumor mouse models. HMGB3 silence inhibited mammoshpere formation, cell proliferation and CD44+,CD24−, by interacting with HIF1α.
Conclusion: HMGB3 silence could inhibit the cell proliferation in vitro and suppress tumor growth in vivo levels. The antitumor effects of HMGB3 silence were mediated by interacting with the HIF1α.

Keywords: HMGB3, breast cancer, HIF1α, mammosphere, proliferation

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