circNHSL1 inhibits proliferation and promotes apoptosis of human breast cancer cell line through regulating miR-125b-5p/HMGB3 axis

doi:10.16352/j.issn.1001-6325.2024.12.1678

Abstract

Abstract: Objective To investigate the regulation of miR-125b-5p/HMGB3 axis by circNHSL1 on the biological behavior of breast cancer cells. Methods The breast cancer cells T47D were divided into si-NC group, si-circNHSL1 group, miR-NC group, and miR-125b-5p mimic group and si-circNHSL1+miR-125b-5p inhibitor group. The expression of circNHSL1 and miR-125b-5p in breast cancer tissues and adjacent tissues was determined using RT-qPCR. Western blot was conducted to detect the protein expression of high mobility group protein 3 (HMGB3). Dual luciferase reporter gene assay was used to confirm the interaction between circNHSL1 and miR-125b-5p, miR-125b-5p and HMGB3. The proliferation rate was measured by CCK-8 method; the colony formation assay was applied to detect the colony formation numbers; flow cytometry was used to measure cell apoptosis rate; Transwell assay was used to detect the numbers of migratory and invasive cells. Results Compared with adjacent tissues, circNHSL1 and HMGB3 expression in breast cancer tissues was significantly increased (P＜0.05), while the expression of miR-125b-5p was significantly decreased (P＜0.05). miR-125b-5p directly bound to circNHSL1 and HMGB3, respectively. The circNHSL1 knockdown down regulated circNHSL1 and HMGB3 expression and upregulated miR-125b-5p expression in T47D cells (P＜0.05). After transfection with miR-125b-5p mimic, miR-125b-5p expression was up-regulated and HMGB3 expression was down-regulated (P＜0.05). Moreover, transfection of miR-125b-5p inhibitor reversed the effect of circNHSL1 silencing on the expression of miR-125b-5p and HMGB3. Low expression of circNHSL1 or high expression of miR-125b-5p increased the cell inhibition rate, colony formation and apoptosis rate of T47D and decreased the number of migratory and invasive cells (P＜0.05). Moreover, transfection of miR-125b-5p inhibitor saved the effect of circNHSL1 silencing on cell phenotypes (P＜0.05). Conclusions Interfering with circNHSL1 might promote cell apoptosis and inhibit cell proliferation, migration and invasion in breast cancer cell by up-regulating the miR-125b-5p/HMGB3 axis.

Key words: breast cancer, circNHSL1, miR-125b-5p, high mobility group protein 3(HMGB3)

CLC Number:

R730.2

LI Huan, XIE Xianxin. circNHSL1 inhibits proliferation and promotes apoptosis of human breast cancer cell line through regulating miR-125b-5p/HMGB3 axis[J]. Basic & Clinical Medicine, 2024, 44(12): 1678-1684.

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