Anticancer bioactive peptide inhibits gastric cancer progression by regulating the long non-coding RNA MIR22HG

Anticancer bioactive peptide (ACBP), a novel antitumor agent isolated from goat liver immunized with a human gastric cancer (GC) extract in our lab, shows significant and effective inhibition of tumor cell proliferation in GC. Long noncoding RNAs (LncRNAs) have been shown to play a key role in the progression of GC. However, the regulatory effect of ACBP on LncRNA for Gastric cancer (GC) remains unclear. This study investigated the potential preventive and therapeutic role of the ACBP-regulated MIR22HG. The biological roles of ACBP in GC cells were assessed using CCK-8 and EDU assays. The effect of ACBP on tumor growth was determined by a subcutaneous xenograft model.Methylation analysis, RNA pull-down assay, RNA immunoprecipitation (RIP) assay, and chromatin immunoprecipitation assays were performed to evaluate the function and mode of action of the LncRNA MIR22HG/ protein arginine methyltransferase 5 (PRMT5) /FOXP1 axis. In this study, we found that ACBP can inhibit GC cell proliferation and invasion in vitro and in vivo. ACBP upregulates LncRNA MIR22HG expression by suppressing the enrichment of EZH2 and H3K27me3 on the LncRNA MIR22HG promoter. The LncRNA MIR22HG activates FOXP1 transcription by recruiting the PRMT5 transcription factor to the FOXP1 promoter region. These results indicate that ACBP upregulates LncRNA MIR22HG and regulates FOXP1 to inhibit gastric cancer proliferation and migration, suggesting that it may play an essential role in predicting clinical outcome.本实验室从经人胃癌（Gastric Cancer, GC）提取物免疫的山羊肝脏中分离得到一种新型抗肿瘤剂——抗癌生物活性肽（Anticancer bioactive peptide, ACBP），其对胃癌细胞增殖具有显著抑制作用。长链非编码RNA（Long noncoding RNAs, LncRNAs）已被证实可在胃癌进展中发挥关键调控作用。然而，ACBP对胃癌相关长链非编码RNA的调控效应仍不明确。本研究探究了ACBP调控的MIR22HG的潜在预防与治疗价值。采用CCK-8实验与EDU实验评估ACBP在胃癌细胞中的生物学功能；通过皮下移植瘤模型检测ACBP对肿瘤生长的影响。通过甲基化分析、RNA拉取实验、RNA免疫沉淀（RNA immunoprecipitation, RIP）实验及染色质免疫沉淀实验，解析长链非编码RNA MIR22HG/蛋白质精氨酸甲基转移酶5（Protein Arginine Methyltransferase 5, PRMT5）/FOXP1通路的功能与作用机制。本研究发现，ACBP可在体外与体内抑制胃癌细胞的增殖与侵袭。ACBP通过抑制增强子zeste同源物2（Enhancer of Zeste Homolog 2, EZH2）与组蛋白H3赖氨酸27三甲基化（Histone H3 Lysine 27 Trimethylation, H3K27me3）在MIR22HG启动子区域的富集，上调长链非编码RNA MIR22HG的表达。长链非编码RNA MIR22HG可通过招募转录因子PRMT5至FOXP1启动子区域，激活FOXP1的转录。上述结果表明，ACBP可通过上调MIR22HG的表达并调控FOXP1，进而抑制胃癌细胞的增殖与迁移，提示其或可作为临床预后预测的潜在关键标志物。