PDHA1 promotes proliferation,invasion and metastasis of triple-nega-tive breast cancer cells
10.3969/j.issn.1000-4718.2024.02.007
- VernacularTitle:PDHA1促进三阴性乳腺癌细胞的增殖、侵袭和转移
- Author:
Jiaqi LI
1
;
Yong SUN
;
Le LI
;
Yuan LI
;
Jun FAN
;
Zhihua KONG
;
Xiaoyun MAO
;
Yong DAI
Author Information
1. 暨南大学基础医学与公共卫生学院医学生物化学与分子生物学系,广东 广州 510632
- Keywords:
triple-negative breast cancer;
pyruvate dehydrogenase E1 subunit alpha1;
cell proliferation;
tu-mor metastasis;
epithelial-mesenchymal transition
- From:
Chinese Journal of Pathophysiology
2024;40(2):244-254
- CountryChina
- Language:Chinese
-
Abstract:
AIM:One of the important characteristics of the occurrence and development of triple-negative breast cancer(TNBC)is dysregulated cell metabolism.The aim of this study is to investigate the mechanism of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),a key enzyme component in aerobic glycolysis,affecting the proliferation,metastasis and invasion of TNBC.METHODS:(1)The expression levels of PDHA1 in breast cancer tissues and adja-cent tissues were analyzed by UALCAN database,KM-plotter database,Gene MANIA database and TCGA database.The expression of PDHA1 was compared according to tumor pathological stage,subtype classification and breast cancer bio-markers.The function of PDHA1 in TNBC was explored by gene enrichment analysis.(2)Immunohistochemistry assays were used to detect the expression of PDHA1 in human TNBC tissue and adjacent tissue samples.(3)Stable PDHA1 knockout and PDHA1 rescue TNBC MDA-MB-231 cells were constructed.The proliferation of MDA-MB-231 cells was de-tected by colony formation assay and cell counting assay.The regulatory effect of PDHA1 on the invasion and migration of MDA-MB-231 cells was detected by in vitro scratch assay and Transwell migration assay.RESULTS:Database analysis showed that the group with high PDHA1 expression in breast cancer had shorter survival and worse prognosis.In clinical specimens,the expression of PDHA1 in cancer tissues was higher than that in adjacent normal tissues.Knockout of PDHA1 inhibited the proliferation,metastasis,invasion and epithelial-mesenchymal transition of MDA-MB-231 cells.CONCLUSION:PDHA1 is overexpressed in TNBC,and it promotes cell proliferation and facilitates TNBC metastasis through the epithelial-mesenchymal transition pathway.
