期刊
LIFE SCIENCES
卷 241, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2019.117114
关键词
LSD1; TSPAN8; EMT; H3K9me2; Colorectal cancer
资金
- Beijing Natural Science Foundation [7192014]
- Open Project of Key Laboratory of Genomics and Precision Medicine, Chinese Academy of Sciences
- National Laboratory of Biomacromolecules [2017kf02]
- Practical Training Plan for the Cross Training of High Level Talents in Beijing Universities [2017271]
- Importation and Development of HighCaliber Talents Project of Beijing Municipal Institutions [CIT TCD201304054]
- National Natural Science Foundation of China [30800580]
Aims: Colorectal cancer (CRC) is the fourth leading cause of cancer-related mortality worldwide. Over-expression of tetraspanin 8 (TSPAN8) is related to the development and progression of CRC. Whether TSPAN8 plays a role in the growth of colorectal cancer and its epigenetic mechanisms regulated by Lysine Specific Demethylase 1 (LSD1) are still unknown. Main methods: In this study, RT-PCR and western blotting were used to analyze the mRNA and protein expression, respectively; cell viability was assayed with MTS analysis; cell migration was measured with Trans-well analysis. Key findings: In the present study, the results indicated that the mRNA levels of LSD1 and TSPAN8 in CRC were significantly higher than that in corresponding adjacent non-tumor tissue. Down-regulation of LSD1 or TSPAN8 as well as LSD1 inhibitor Tranylcypromine hemisulfate inhibited the proliferation and migration of CRC cells, while over-expression of LSD1 exhibited opposite effects. LSD1 up-regulated TSPAN8 expression and reduced H3K9me2 occupancy on the TSPAN8 promoter in CRC cells. TSPAN8 promoted epithelial-mesenchymal transition (EMT) in CRC cells in LSD1-dependent manner. Significance: TSPAN8 may be considered as a promising biomarker for the diagnosis and prognosis in patients with CRC. Furthermore, TSPAN8 could be a novel therapeutic target and potent LSD1 inhibitors could be designed and developed in the treatment of CRC.
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