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

Abstract

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.

The circBVES&nbsp;Acts as a Sponge of miR-145-5p&nbsp;to Promote Gastric Cancer Glycolysis and Progression Through Regulating HMGB3&nbsp;Expression

“…We also found that HMGB3 was over-expressed in GC and negatively correlated with miR-145-5p. Consistent with our results, it has been reported that HMGB3 is highly expressed in breast cancer, colorectal cancer and glioblastoma, and can regulate the development of tumors [35][36][37]. To verify the relationship between circBVES and HMGB3, we found that low expression of circBVES inhibited HMGB3 expression at mRNA and protein levels.…”

Biological functions and theranostic potential of HMGB family members in human cancers

“…156 Later research revealed that this mediation could be strengthened by HMGB3. 157 Clinical significance of HMGB family members in human cancers HMGB family members are widely involved in carcinogenesis, increasing evidence also indicate that HMGB family members are promising targets for cancer treatment. Moreover, the diagnostic and prognostic roles of HMGB family members are gradually revealed.…”

Establishment of a novel cell cycle-related prognostic signature predicting prognosis in patients with endometrial cancer

“…Research by Zhang et al proved that overexpressed HMGB3 promoted proliferation and migration of cancer cells, accelerating the progression of colorectal cancer [ 25 ]. Studies by Gu et al demonstrated that silencing HMGB3 expression suppressed breast cancer cell proliferation, thus inhibited tumor growth [ 26 ]. It has been proved that the regulation of HMGB3 by tumor suppressive miR-205-5p suppressed cancer cell aggressiveness and participated in prostate cancer progression [ 27 ].…”