期刊
CANCER LETTERS
卷 533, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2022.215595
关键词
HOXB9; DNMT1; Cell cycle; RBL2; Pancreatic cancer
类别
资金
- National Natural Science Foundation of China [82173233, 81872427, 82102858]
- Applied technology research and development Program of Heilongjiang Province [GA19C002]
- Nn 10 Excellent Discipline Construction Program [Hepatobiliary and Pancreatic Tumor 2017]
- Basic scientific research projects of universities in Heilongjiang Province [2020-KYYWF-1465]
- Haiyan Research Fund of Harbin Medical University Cancer Hospital [JJZD2020-03, JJMS2022-04, JJQN2021-05]
- Harbin Medical University Research and Practice Innovation Project [YJSCX2020-51HYD]
- [Nn 10]
In pancreatic cancer, the expression of HOXB9 is down-regulated, while higher expression of HOXB9 is associated with higher survival rates. Over-expression of HOXB9 inhibits pancreatic cancer cell proliferation by regulating RBL2 and cMyc to block cell cycle progression. DNMT1 in pancreatic cancer inhibits the expression of HOXB9 through methylation of its promoter.
Homeobox B9 (HOXB9) is involved in the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of HOXB9 in pancreatic cancer have yet to be identified. In this study, we find that both HOXB9 mRNA and protein levels are down-regulated in pancreatic cancer tissues and cell lines. Kaplan-Meier survival plots of 150 pancreatic cancer cases show that higher expression of HOXB9 in pancreatic cancer patients is associated with higher survival rates. We also find that over-expression of HOXB9 inhibits pancreatic cancer cell proliferation both in cell lines and the nude mouse xenograft as well as PDX models. Applying cell cycle PCR array analysis, Flow CytoMetry, ChIP-qPCR, and luciferase experiments, we observe that HOXB9 blocks cell cycle progression in the G0/G1 phase via up-regulating RBL2 and inhibiting cMyc, and we further find that DNMT1 inhibits the expression of HOXB9 in pancreatic cancer by promoting the methylation of its promoter. Our findings highlight a novel mechanism of the DNMT1/HOXB9/RBL2/c-Myc pathway in regulating the cell cycle and proliferation of pancreatic cancer cells and provide a research basis for the prognosis and therapeutic application of HOXB9 in pancreatic cancer.
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