Experimental Study Of RIPK3 Inhibiting The Occurrence And Development Of Spontaneous Intestinal Tumors

Background:Receptor interacting protein 3（RIPK3）,a member of serine/threonine protein kinase family,plays a key regulatory role in programmed cell necrosis.Studies have shown that RIPK3 plays a key role in tumors,and the down-regulation of RIPK3 expression is related to the poor prognosis of many tumor types.Colorectal cancer is one of the high incidence cancers in the world,and the mortality rate has long occupied a high position in the country.However,the role of RIPK3 in the occurrence and development of colorectal cancer is not clear.Objective:To study the role and mechanism of RIPK3 in spontaneous intestinal tumorigenesis,and to explore the clinical value of RIPK3.Methods:The expression levels of RIPK3 in normal intestinal samples and intestinal tumor samples in cancer transcriptome database were analyzed.The mouse model of spontaneous intestinal tumor and RIPK3 knockout（RIPK3-/-）mice were established with APC gene mutant mice（APCmin/+）,the role of RIPK3 knockout in the occurrence and development of intestinal tumor in APCmin/+ mice was studied,and the progression of intestinal tumor in APCmin/+RIPK3-/-mice and APCmin/+ mice was analyzed and compared;Then,the protein expression level related to cell proliferation was detected by Western blotting;The m RNA expression level of related genes was detected by real-time fluorescence quantitative PCR.The mechanism and function of RIPK3 in the occurrence and development of spontaneous intestinal tumors were verified by blocking the receptor.Results:It was found that the expression of RIPK3 decreased in colorectal cancer patients,and the prognosis of colorectal cancer patients with low expression of RIPK3 was poor;RIPK3 knockout further aggravated the occurrence and development of spontaneous intestinal tumors in APCmin/+ mice;By detecting the signal pathway,it was found that IL-6/STAT3 signal pathway was activated in APCmin/+RIPK3-/-mouse model,which promoted the proliferation of tumor cells and inhibited apoptosis.Anti-IL-6R antibody can weaken the intestinal tumor progression of APCmin/+RIPK3-/-mice.Conclusion:（1）The prognosis of colorectal cancer patients with low expression of RIPK3 may be worse;（2）RIPK3 plays an inhibitory role in the occurrence and development of spontaneous colorectal cancer;（3）RIPK3 inhibits the occurrence and development of spontaneous intestinal tumors by inhibiting the over activation of IL-6/STAT3.