The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a well characterised tumour suppressor, playing a critical role in the maintenance of fundamental cellular processes including cell proliferation, migration, metabolism, and survival. Subtle decreases in cellular levels of PTEN result in the development and progression of cancer, hence there is tight regulation of the expression, activity, and cellular half-life of PTEN at the transcriptional, post-transcriptional, and post-translational levels.PTENP1, the processed pseudogene ofPTEN, is an important transcriptional and post-transcriptional regulator ofPTEN. PTENP1expression produces sense and antisense transcripts modulatingPTENexpression, in conjunction with miRNAs. Due to the high sequence similarity betweenPTENand thePTENP1sense transcript, the transcripts possess common miRNA binding sites with the potential forPTENP1to compete for the binding, or ‘sponging’, of miRNAs that would otherwise target thePTENtranscript.PTENP1therefore acts as a competitive endogenous RNA (ceRNA), competing withPTENfor the binding of specific miRNAs to alter the abundance of PTEN. Transcription from the antisense strand produces two functionally independent isoforms (PTENP1-AS-αandPTENP1-AS-β), which can regulatePTENtranscription. In this review, we provide an overview of the post-transcriptional regulation ofPTENthrough interaction with its pseudogene, the cellular miRNA milieu and operation of the ceRNA network. Furthermore, its importance in maintaining cellular integrity and how disruption of thisPTEN–miRNA–PTENP1axis may lead to cancer but also provide novel therapeutic opportunities, is discussed. Precision targeting ofPTENP1-miRNA mediated regulation ofPTENmay present as a viable alternative therapy.
染色体10上缺失的磷酸酶与张力蛋白同源物（PTEN）是一种特征明确的肿瘤抑制因子，在维持细胞增殖、迁移、代谢和存活等基本细胞过程中发挥关键作用。PTEN细胞水平的轻微下降会导致癌症的发生和发展，因此PTEN在转录、转录后和翻译后水平上的表达、活性和细胞半衰期受到严格调控。PTEN的加工假基因PTENP1是PTEN重要的转录和转录后调节因子。PTENP1的表达会产生正义和反义转录本，与微小RNA（miRNA）共同调节PTEN的表达。由于PTEN与PTENP1正义转录本之间具有高度序列相似性，这些转录本拥有共同的miRNA结合位点，使得PTENP1有可能竞争性结合或“吸附”那些原本靶向PTEN转录本的miRNA。因此，PTENP1作为一种竞争性内源RNA（ceRNA），通过与PTEN竞争结合特定miRNA来改变PTEN的丰度。反义链的转录产生两种功能独立的亚型（PTENP1-AS-α和PTENP1-AS-β），它们能够调节PTEN的转录。本文综述了PTEN通过与其假基因相互作用、细胞miRNA环境以及ceRNA网络的运作所实现的转录后调控。此外，文章还探讨了这种调控在维持细胞完整性方面的重要性，以及PTEN–miRNA–PTENP1轴的破坏如何可能导致癌症，同时也可能提供新的治疗机会。精准靶向PTENP1-miRNA介导的PTEN调控可能成为一种可行的替代疗法。
PTEN,PTENP1, microRNAs, and ceRNA Networks: Precision Targeting in Cancer Therapeutics
肿瘤(癌症)患者之家