KIAA0101 Promotes Breast Cancer Progression through P53-Mediated Metabolic Reprogramming

Abstract

Background: The altered metabolism contributes to the metabolic reprogramming of tumor microenvironment, thus promoting the growth and proliferation of tumor cells. This study aimed to explore the mechanism of KIAA0101 in promoting the development of breast cancer (BC) through metabolic reprogramming. Methods: In this study, the expression of KIAA0101 in BC patients was measured using quantificational Real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) and Immunohistochemistry. The BC tumor mice model was constructed by subcutaneous injection of MDA-MB-231 cells and divided into the MDA-MB-231+si-NC (siRNA negative control) group and the MDA-MB-231+si-KIAA0101 group. The tumor volume of the BC mice model in the two groups was measured once a week to investigate the effect of KIAA0101 on tumor growth. The function of KIAA0101 and P53 on the migration and invasion of MDA-MB-231 cells in vitro was examined by Transwell assay. The glucose and lipid metabolism-related protein expressions in BC cells were measured by Western blot and qRT-PCR. Furthermore, the effects of glucose concentration and incubation time on the expression of KIAA0101 in BC cells were determined by qRT-PCR. Results: Both BC patients and mouse models exhibited overexpression of KIAA0101 (p < 0.05). This overexpression led to an increase in cell migration and invasion in vitro (p < 0.05). Conversely, P53 showed a contrasting trend to KIAA0101 in BC cells (p < 0.05). In addition, glucose incubation enhanced the expression of KIAA0101 in BC cells (p < 0.05), and the knockdown of KIAA0101 inhibited energy metabolism in BC cells (p < 0.05). The protein and mRNA expressions of the glucose transporter type 1 (GLUT1), pyruvate kinase M2 (PKM2), and hypoxia-inducible factor-1 (HIF-1) were decreased in KIAA0101-depleted cells (p < 0.05) but increased in P53-depleted cells (p < 0.05). Furthermore, si-KIAA0101 effectively inhibited the tumor volume and growth rate of BC mice model (p < 0.05). Conclusions: KIAA0101 regulates breast cancer progression through a mechanism involving metabolic reprogramming induced by P53.