Open AccessLactate induced up‐regulation of KLHDC8A (Kelch domain‐containing 8A) contributes to the proliferation, migration and apoptosis of human glioma cells
Author(s) -
Zhu Xiaolong,
Chen Tianbing,
Yang Hui,
Lv Kun
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15780
Subject(s) - glioma , gene knockdown , cancer research , apoptosis , mmp2 , cell growth , cell cycle , mapk/erk pathway , biology , downregulation and upregulation , p38 mitogen activated protein kinases , microbiology and biotechnology , chemistry , signal transduction , gene , biochemistry
Abstract Glioma is a common type of malignant brain tumour with high mortality and relapse rate. However, the molecular mechanisms of glioma development have not been clarified. Differentially expressed genes in normal brain tissues and glioma tissues, low‐grade and high‐grade gliomas were screened out with GEO database analysis. We found that KLHDC8A (Kelch domain‐containing 8A) expression level was significantly increased in high‐grade glioma tissues and that high KLHDC8A expression was closely related with poor prognosis. Function assays indicated that KLHDC8A knockdown inhibited proliferation, migration and invasion, blocked the cell cycle and promoted apoptosis in glioma cells. Mechanistically, KLHDC8A regulated various functions in glioma by directly mediating Bcl2, BAX, p21, CDK2, MMP2 transcription and ERK and P38 MAPK activation. KLHDC8A overexpression enhances glioma tumorgenesis such as cell proliferation, migration and invasion. The ERK and P38 MAPK which activated by KLHDC8A overexpression could be reversed by U0126 and SB203580, respectively. Meanwhile, stimulation of lactate which produced by glycolysis is responsible for induction of KLHDC8A expression. Collectively, we demonstrated that KLHDC8A plays an important role in tumorgenesis of glioma, suggesting that it is a promising prognostic marker and a potential therapy target for the treatment of glioma.