中国病理生理杂志2024,Vol.40Issue(2):244-254,11.DOI:10.3969/j.issn.1000-4718.2024.02.007
PDHA1促进三阴性乳腺癌细胞的增殖、侵袭和转移
PDHA1 promotes proliferation,invasion and metastasis of triple-nega-tive breast cancer cells
摘要
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.关键词
三阴性乳腺癌/丙酮酸脱氢酶E1亚基α1/细胞增殖/肿瘤转移/上皮-间充质转化Key words
triple-negative breast cancer/pyruvate dehydrogenase E1 subunit alpha1/cell proliferation/tu-mor metastasis/epithelial-mesenchymal transition分类
医药卫生引用本文复制引用
李佳琪,孙勇,李乐,李媛,范骏,孔之华,毛晓韵,戴勇..PDHA1促进三阴性乳腺癌细胞的增殖、侵袭和转移[J].中国病理生理杂志,2024,40(2):244-254,11.基金项目
国家自然科学基金资助项目(No.81974430) (No.81974430)
国家中医优势专科建设项目(No.2023104) (No.2023104)
广东省自然科学基金(No.2023A1515010578 ()
No.2019A1515012037) ()
广东省中医药重点学科(临床类)建设项目(No.1002042801) (临床类)
佛山市"十四五"高水平医学重点专科项目(No.2021107) (No.2021107)
佛山市"十四五"中医重点专科项目(No.202015) (No.202015)
佛山市南海区"十四五"高水平医学重点专科项目(No.2021211) (No.2021211)