Research progress of lysine-specific demethylase 1-mediated classical Wnt/β-catenin signaling pathway in cancers
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    Abstract:

    As a global public health issue, cancer is one of the major diseases that endanger human health in the world today. According to the latest cancer statistics released by the National Cancer Center in 2019, there were 3.929 million new patients with malignant tumor in China in 2015, with a death rate of 2.338 million, an incidence rate of 2.8583/100 000 and a mortality rate of 1.705/100 000. The occurrence and development of tumor is a multi-factor, multi-gene, multi-stage progressive cumulative evolution process, involving tumor transformation, survival, proliferation, invasion, angiogenesis and metastasis. This process is accompanied by genetic and epigenetic changes: oncogenes, tumor suppressor genes, mismatch repair genes, cell adhesion molecules are changed at DNA, RNA and protein levels. Although tumor diagnosis and treatment techniques have made continuous progress in recent years, most patients are already in advanced stage and the overall prognosis is poor. So, it is significant to explore the pathogenesis of cancer and find more effective prevention and treatment methods. Existing researches show that epigenetic changes are of great significance in tumor occurrence, development, invasion and metastasis. It’s known that epigenetic modifications mainly include histone modification, DNA methylation, nucleosome remodeling, non-coding RNA, etc. In eukaryotes, histone modification includes acetylation, methylation, phosphorylation, ribosylation and ubiquitination, etc. Like other histone modifications, histone methylation is a dynamic and reversible process. Lysine-specific demethylase 1 (LSD1) can specifically catalyze the demethylation and dimethyl reactions of lysine at position 4 (H3K4) and lysine at position 9 (H3K9) of histone H3, and interact with histone deacetylase to act as a transcription repressor. This enzyme is crucial to the growth and development of mammals and participates in a variety of biological processes, including cell differentiation, formation of heterochromatin, reasonable maintenance of DNA methylation status in cells and induction of formation of pluripotent stem cells, etc. At present, it is confirmed that LSD1 is highly expressed in various malignant tumor tissues and plays an important role in the occurrence, development and drug resistance of tumors. Wnt signaling pathway is a highly conserved signaling pathway in evolution, which plays an important role in cell proliferation, differentiation, migration and apoptosis. Gene mutation of key molecules of Wnt signaling pathway plays an important role in the occurrence and development of tumors. Although LSD1 and Wnt signaling pathways are both related to tumor occurrence and development, whether there is a link between them has not been clarified. In recent years, more and more studies have shown that LSD1 can affect the occurrence and development of tumors by regulating the activity of classical Wnt signaling pathway. In this review, the authors summarize the new research findings in the LSD1-mediated Wnt/β-catenin signaling pathway in cancers.

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FAN Fei, , DING Jie, LIU Zhenhua, WU Ming, JIANG Zhuan, , LIU Hang, LI Xian, ZENG Jiaxing, ZHANG Lin. Research progress of lysine-specific demethylase 1-mediated classical Wnt/β-catenin signaling pathway in cancers[J]. Chin J Gen Surg,2020,29(4):480-486.
DOI:10.7659/j. issn.1005-6947.2020.04.012

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History
  • Received:September 20,2019
  • Revised:March 13,2020
  • Adopted:
  • Online: April 25,2020
  • Published: