Epigenetic alterations have been reported to play critical roles in the development of colorectal cancer (CRC). However, the biological function of the lysine-specific histone demethylase 1B (LSD2/KDM1B) in CRC is not well understood. Therefore, we investigated the characteristics of LSD2 in CRC. We observed significant upregulation of LSD2 in CRC tissue compared to that in normal colorectal tissue. LSD2 promotes CRC cell proliferation and inhibits cell apoptosis through cell cycle regulation, promoting CRC progression both in vitro and in vivo. We found that LSD2 performs these functions by inhibiting the p53-p21-Rb pathway. Finally, we found that LSD2 directly binds to p53 and represses p53 expression via H3K4me2 demethylation at the p53 promoter. Our results revealed that LSD2 acts as an oncogene by binding and inhibiting p53 activity in CRC. Thus, LSD2 may be a new molecular target for CRC treatment.

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The present study aimed to investigate the effects of c‐Ski on cell proliferation, invasion and migration of gastric cancer associated fibroblasts (CAFs). Expression of c‐Ski in gastric cancer (GC) tissues was determined using immunohistochemistry. Both CAFs and non‐cancerous gastric fibroblasts (NGFs) were isolated and cultured. c‐Ski and Smad3 were over‐expressed or knocked down using pcDNA3.0‐c‐Ski/Smad3 or siRNA, respectively. Cell viability, invasion and migration were measured and expression of c‐Ski, α‐SMA, and Smad3 in cells was determined using real time quantitative PCR (RT‐qPCR) and Western blotting. Expression of c‐Ski was significantly higher in both in GC tissues and cell lines, and was the highest in tissues of diffuse type. Both c‐Ski and α‐SMA were significantly over‐expressed in CAFs compared with that in the NGFs. When c‐Ski was over‐expressed in NGFs, cell viability, cell invasion and migration were all enhanced and expression of Smad3 was downregulated. When c‐Ski was inhibited, cell viability, cell invasion, and migration were all suppressed and expression of Smad3 was upregulated. Meanwhile, overexpression of Smad3 significantly reversed the effects of over‐expressed c‐Ski in NGFs, and knockdown of Smad3 dramatically reversed the effects of si‐c‐Ski in CAFs. Over‐expressed c‐Ski could enhance cell viability, promote cell invasion, and migration of GC CAFs, and the effects might be through regulation of Smad3 signaling. This study may give deeper insights for relationship between c‐Ski and CAFs, as well as role of c‐Ski in cancer development, and also provide some novel research targets for treatment of GC.