DPY30 knockdown suppresses colorectal carcinoma progression via inducing Raf1/MST2-mediated apoptosis
HaiFeng Jiang,
WeiChao Su,
HaiXing Wang,
ChunYing Luo,
YaTao Wang,
LinJun Zhang,
LingTao Luo,
ZeBin Lu,
DongYan Shen,
GuoQiang Su
Affiliations
HaiFeng Jiang
Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian Province, China; Department of Critical Care Medicine, Second People's Hospital of Yibin City, Yibin, 644000, Sichuan Province, China
WeiChao Su
Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian Province, China; Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, 361012, China
HaiXing Wang
Department of Endoscopy Center, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
ChunYing Luo
Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, China
YaTao Wang
Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian Province, China
LinJun Zhang
Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China
LingTao Luo
Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian Province, China
ZeBin Lu
Department of Clinical Medicine, Fujian Medical University, Fuzhou, 350122, China
DongYan Shen
Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China; Corresponding author.
GuoQiang Su
Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian Province, China; Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, China; Department of Clinical Medicine, Fujian Medical University, Fuzhou, 350122, China; Corresponding author. Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian Province, China.
Colorectal Carcinoma (CRC) is one of the most common malignant tumors of the digestive tract, with a high mortality rate. DPY30 is one of the core subunits of the histone methyltransferase complex, which was involved in many cancer processes. However, the role of DPY30 in the occurrence and progression of CRC remains unclear. In this study, we sought to evaluate the role and mechanism of DPY30 in CRC cells apoptosis. Here, we identified that knockdown of DPY30 significantly inhibited the HT29 and HCT116 cells proliferation in vitro. Moreover, the knockdown of DPY30 significantly increased the apoptosis rate and promoted the expression of apoptosis-related proteins in CRC cells. Meanwhile, DPY30 knockdown promoted CRC cells apoptosis through endogenous programmed death and in a caspase activation-dependent manner. Furthermore, RNA-seq analysis revealed that the action of DPY30 is closely related to the apoptosis biological processes, and screened its potential effectors Raf1. Mechanistically, DPY30 downregulation promotes MST2-induced apoptosis by inhibiting Raf1 transcriptional activity through histone H3 lysine 4 trimethylation (H3K4me3). In vivo experiments showed that DPY30 was correlated with Raf1 in nude mouse subcutaneous xenografts tissues significantly. Clinical colorectal specimens further confirmed that overexpression of DPY30 in malignant tissues was significantly correlated with Raf1 level. The vital role of the DPY30/Raf1/MST2 signaling axis in the cell death and survival rate of CRC cells was disclosed, which provides potential new targets for early diagnosis and clinical treatment of CRC.
