Li Penghui, Xue Yuan, Gu Xinyu
Department of Gastrointestinal surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, Henan, China.
Department of thyroid surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, Henan, China.
Cancer Cell Int. 2025 Jul 2;25(1):244. doi: 10.1186/s12935-025-03889-6.
Cancers of the digestive tract, including those affecting the esophagus, stomach, liver, pancreas, and colorectum, impose a substantial global health burden due to their high morbidity and mortality rates. Despite advancements in diagnostic and treatment modalities, the molecular mechanisms underpinning the initiation and progression of digestive tract cancers remain incompletely understood. Recent progress in high-throughput sequencing technology has uncovered the crucial role of small non-coding RNAs (ncRNAs) in regulating gene expression and maintaining genomic stability across various cancers, including those affecting the digestive tract. P-element-induced wimpy testis (PIWI)-integrating RNAs (piRNAs), a subset of small ncRNAs, emerge as pivotal regulators in preserving genome integrity by suppressing transposable elements in germline cells. Growing evidence implicates piRNAs in the development and advancement of digestive tract cancers. Notably, piRNAs exhibit complex and multifaceted roles in these tumors, functioning as both tumor suppressors and oncogenes. They exert their effects through diverse mechanisms, including post-transcriptional gene silencing, epigenetic modifications, and modulation of signaling pathways involved in tumorigenesis, such as the Wnt/β-catenin, PI3K/Akt, and MAPK pathways. Dysregulation of piRNAs disrupts key cellular processes, including cell cycle regulation, apoptosis, epithelial-mesenchymal transition, and metastasis, across various digestive tract cancers. Moreover, distinct expression profiles of specific piRNAs correlate with diverse clinical features and outcomes in individuals afflicted with digestive tract cancers, highlighting their potential as diagnostic and prognostic biomarkers in this context. Furthermore, therapeutic interventions targeting dysregulated piRNAs or their downstream effectors hold promise as novel avenues for precision medicine approaches in managing digestive tract cancers. In this review, we summarize the current understanding of piRNAs in digestive tract cancers, focusing on their dual roles as both tumor suppressors and oncogenes. We further delve into the intricate molecular mechanisms by which piRNAs modulate crucial cellular processes implicated in tumorigenesis. Additionally, we explore the potential of piRNAs as valuable diagnostic, prognostic, and therapeutic biomarkers in the landscape of digestive tract cancers. By elucidating the complex interplay between piRNAs and digestive tract cancers, this review aims to offer insights into novel therapeutic strategies centered around targeting piRNAs for precision medicine approaches in the management of these malignancies.
消化道癌症，包括影响食管、胃、肝、胰腺和结肠直肠的癌症，因其高发病率和死亡率而给全球健康带来沉重负担。尽管诊断和治疗方式取得了进展，但消化道癌症发生和进展的分子机制仍未完全明了。高通量测序技术的最新进展揭示了小非编码RNA（ncRNA）在调节基因表达和维持包括消化道癌症在内的各种癌症基因组稳定性方面的关键作用。P元件诱导的微弱睾丸（PIWI）互作RNA（piRNA）是小ncRNA的一个子集，通过抑制生殖细胞中的转座元件，成为维持基因组完整性的关键调节因子。越来越多的证据表明piRNA与消化道癌症的发生和发展有关。值得注意的是，piRNA在这些肿瘤中发挥着复杂而多方面的作用，既作为肿瘤抑制因子，又作为癌基因。它们通过多种机制发挥作用，包括转录后基因沉默、表观遗传修饰以及调节参与肿瘤发生的信号通路，如Wnt/β-连环蛋白、PI3K/Akt和MAPK通路。piRNA的失调会破坏各种消化道癌症中的关键细胞过程，包括细胞周期调节、细胞凋亡、上皮-间质转化和转移。此外，特定piRNA的不同表达谱与消化道癌症患者的各种临床特征和预后相关，突出了它们在这种情况下作为诊断和预后生物标志物的潜力。此外，针对失调的piRNA或其下游效应器的治疗干预有望成为消化道癌症精准医学方法的新途径。在这篇综述中，我们总结了目前对piRNA在消化道癌症中的认识，重点关注它们作为肿瘤抑制因子和癌基因的双重作用。我们进一步深入探讨piRNA调节与肿瘤发生相关的关键细胞过程的复杂分子机制。此外，我们还探讨了piRNA在消化道癌症领域作为有价值的诊断、预后和治疗生物标志物的潜力。通过阐明piRNA与消化道癌症之间的复杂相互作用，本综述旨在为围绕靶向piRNA的精准医学方法管理这些恶性肿瘤的新型治疗策略提供见解。
