Specificity Proteins/Krüppel-like Factors (SP/KLF family) are a conserved family of transcriptional regulators. These proteins share three highly conserved, contiguous zinc fingers in their carboxy-terminus, requisite for binding to cis elements in DNA. Each SP/KLF protein has unique primary sequence within its amino-terminal and carboxy-terminal regions, and it is these regions which interact with co-activators, co-repressors, and chromatin-modifying proteins to support the transcriptional activation and repression of target genes. Krüppel-like Factor 9 (KLF9) and Krüppel-like Factor 13 (KLF13) are two of the smallest members of the SP/KLF family, are paralogous, emerged early in metazoan evolution, and are highly conserved. Paradoxically, while most similar in primary sequence, KLF9 and KLF13 display many distinct roles in target cells. In this article, we summarize the work that has identified the roles of KLF9 (and to a lesser degree KLF13) in tumor suppression or promotion via unique effects on differentiation, pro- and anti-inflammatory pathways, oxidative stress, and tumor immune cell infiltration. We also highlight the great diversity of miRNAs, lncRNAs, and circular RNAs which provide mechanisms for the ubiquitous tumor-specific suppression of KLF9 mRNA and protein. Elucidation of KLF9 and KLF13 in cancer biology is likely to provide new inroads to the understanding of oncogenesis and its prevention and treatments.
特异性蛋白/Krüppel样因子（SP/KLF家族）是一类保守的转录调控因子家族。这些蛋白质在其羧基末端共享三个高度保守且连续排列的锌指结构，该结构是与DNA顺式元件结合所必需的。每个SP/KLF蛋白在其氨基末端和羧基末端区域具有独特的初级序列，正是这些区域通过与共激活因子、共抑制因子及染色质修饰蛋白相互作用，实现对靶基因的转录激活与抑制调控。Krüppel样因子9（KLF9）与Krüppel样因子13（KLF13）是SP/KLF家族中分子量最小的两个成员，二者为旁系同源蛋白，在后生动物进化早期出现且高度保守。矛盾的是，尽管KLF9与KLF13在初级序列上最为相似，它们在靶细胞中却展现出诸多不同的功能。本文综述了KLF9（及次要涉及的KLF13）通过影响细胞分化、促炎与抗炎通路、氧化应激及肿瘤免疫细胞浸润等独特机制，在肿瘤抑制或促进过程中发挥作用的研究进展。同时，我们重点阐述了miRNA、lncRNA和环状RNA通过多种机制普遍性抑制KLF9 mRNA及蛋白表达的多样性。阐明KLF9与KLF13在癌症生物学中的作用，有望为理解肿瘤发生机制及其防治策略提供新的突破口。
肿瘤(癌症)患者之家