The Histone Demethylase KDM3A, Increased in Human Pancreatic Tumors, Regulates Expression of DCLK1 and Promotes Tumorigenesis in Mice
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View abstract on PubMed
Summary
This summary is machine-generated.Histone lysine demethylase 3A (KDM3A) is upregulated in pancreatic cancer and promotes tumor growth by increasing doublecortin calmodulin-like kinase 1 (DCLK1) expression. Targeting KDM3A may offer a new therapeutic strategy for pancreatic cancer.
Area Of Science
- Oncology
- Molecular Biology
- Gene Regulation
Background
- Histone lysine demethylase 3A (KDM3A) is upregulated in various tumors, including pancreatic cancer.
- KDM3A regulates gene transcription by demethylating H3K9me1 and H3K9Me2.
- DCLK1 is a marker of cancer stem cells and its gene is a target of KDM3A.
Purpose Of The Study
- To investigate the role of KDM3A in pancreatic cancer.
- To determine how KDM3A regulates DCLK1 expression.
- To assess the therapeutic potential of targeting KDM3A in pancreatic cancer.
Main Methods
- KDM3A knockdown and overexpression in pancreatic cancer cell lines and non-cancerous cells.
- Assessment of cell migration, invasion, and spheroid formation under varying oxygen conditions.
- Orthotopic tumor growth studies in nude mice.
- Immunohistochemistry, immunoblotting, and RNA-sequencing.
- Analysis of The Cancer Genome Atlas for KDM3A and DCLK1 mRNA levels and patient survival.
Main Results
- KDM3A levels are increased in human pancreatic tumors and cell lines.
- KDM3A knockdown reduced pancreatic cancer cell invasion, migration, and spheroid formation, and slowed tumor growth in mice.
- KDM3A directly regulates DCLK1 expression.
- Overexpression of KDM3A in non-cancerous cells promoted tumor formation and metastasis.
- Hypoxia increased KDM3A expression and sphere formation.
- Elevated KDM3A and DCLK1 mRNA levels correlate with shorter patient survival.
Conclusions
- KDM3A is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and promotes tumor progression.
- KDM3A enhances DCLK1 expression, contributing to cancer stem cell characteristics and tumor aggressiveness.
- Targeting the KDM3A-DCLK1 pathway presents a potential therapeutic strategy for pancreatic cancer.
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