PDF(Pubmed)
Abstract：
KIAA1429, an important component of the N6-methyladenine methyltransferase complex, is involved in the pathology of many types of cancer. In this study, the mechanisms through which KIAA1429 promotes non-small cell lung cancer (NSCLC) progression were explored using in vitro and in vivo experiments. Additionally, bioinformatics analysis of publicly available data was used to determine the relationship between KIAA1429 expression and NSCLC patient survival. The results showed that KIAA1429 was upregulated in NSCLC tissues and cells, and its high expression level was associated with low overall survival. Transcriptome analysis of KIAA1429-silenced NSCLC cells identified 346 differentially expressed genes, which were enriched in ferroptosis and the p53 signaling pathway. KIAA1429 silencing using small interfering (si) RNA promoted erastin-induced ferroptosis in NSCLC cells and activated the p53 signaling pathway. Moreover, si-KIAA1429 inhibited the proliferative, migratory, and invasive abilities of NSCLC cells in vitro and tumor growth in vivo. These in vitro effects were weakened by pifithrin-μ, a p53 inhibitor. Therefore, given its effects on ferroptosis and the p53 signaling pathway, targeting KIAA1429 could be an effective strategy for treating NSCLC.
摘要：
KIAA1429，N6-甲基腺嘌呤甲基转移酶复合物的重要组成部分，与许多类型癌症的病理学有关。在这项研究中,通过体外和体内实验,探讨了KIAA1429促进非小细胞肺癌(NSCLC)进展的机制.此外,对公开数据进行生物信息学分析,以确定KIAA1429表达与NSCLC患者生存之间的关系.结果显示KIAA1429在NSCLC组织和细胞中表达上调,其高表达水平与低总生存率相关。KIAA1429沉默NSCLC细胞的转录组分析鉴定了346个差异表达基因，富含铁凋亡和p53信号通路。使用小干扰(si)RNA的KIAA1429沉默促进了在NSCLC细胞中擦除素诱导的铁凋亡并激活了p53信号通路。此外，si-KIAA1429抑制增殖，迁徙,NSCLC细胞的体外侵袭能力和体内肿瘤生长能力。这些体外作用被吡虫啉-μ削弱，p53抑制剂.因此,鉴于其对铁凋亡和p53信号通路的影响，靶向KIAA1429可能是治疗NSCLC的有效策略.
