Shen Jinze, Su Xinming, Wang Qurui, Ke Yufei, Zheng Tianyu, Mao Yunan, Wang Zehua, Dong Jingyin, Duan Shiwei
Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang 310015, China.
Cancer Pathog Ther. 2023 Sep 5;2(3):142-154. doi: 10.1016/j.cpt.2023.09.001. eCollection 2024 Jul.
Micro ribonucleic acids (miRNAs) are a highly conserved class of single-stranded non-coding RNAs. Within the miR-545/374a cluster, miR-545 resides in the intron of the long non-coding RNA (lncRNA) on Xq13.2. The precursor form, pre-miR-545, is cleaved to generate two mature miRNAs, miR-545-3p and miR-545-5p. Remarkably, these two miRNAs exhibit distinct aberrant expression patterns in different cancers; however, their expression in colorectal cancer remains controversial. Notably, miR-545-3p is affected by 15 circular RNAs (circRNAs) and 10 long non-coding RNAs (lncRNAs), and it targets 27 protein-coding genes (PCGs) that participate in the regulation of four signaling pathways. In contrast, miR-545-5p is regulated by one circRNA and five lncRNAs, it targets six PCGs and contributes to the regulation of one signaling pathway. Both miR-545-3p and miR-545-5p affect crucial cellular behaviors, including cell cycle, proliferation, apoptosis, epithelial-mesenchymal transition, invasion, and migration. Although low miR-545-3p expression is associated with poor prognosis in three cancer types, studies on miR-545-5p are yet to be reported. miR-545-3p operates within a diverse range of regulatory networks, thereby augmenting the efficacy of cancer chemotherapy, radiotherapy, and immunotherapy. Conversely, miR-545-5p enhances immunotherapy efficacy by inhibiting T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) expression. In summary, miR-545 holds immense potential as a cancer biomarker and therapeutic target. The aberrant expression and regulatory mechanisms of miR-545 in cancer warrant further investigation.
微小核糖核酸（miRNA）是一类高度保守的单链非编码RNA。在miR-545/374a簇中，miR-545位于Xq13.2上长链非编码RNA（lncRNA）的内含子中。前体形式pre-miR-545被切割产生两种成熟的miRNA，即miR-545-3p和miR-545-5p。值得注意的是，这两种miRNA在不同癌症中表现出不同的异常表达模式；然而，它们在结直肠癌中的表达仍存在争议。值得注意的是，miR-545-3p受15种环状RNA（circRNA）和10种长链非编码RNA（lncRNA）的影响，它靶向27个参与四条信号通路调控的蛋白质编码基因（PCG）。相比之下，miR-545-5p受一种circRNA和五种lncRNA的调控，它靶向六个PCG并参与一条信号通路的调控。miR-545-3p和miR-545-5p都影响关键的细胞行为，包括细胞周期、增殖、凋亡、上皮-间质转化、侵袭和迁移。虽然低miR-545-3p表达与三种癌症类型的不良预后相关，但关于miR-545-5p的研究尚未见报道。miR-545-3p在多种调控网络中发挥作用，从而提高癌症化疗、放疗和免疫治疗的疗效。相反，miR-545-5p通过抑制含T细胞免疫球蛋白和粘蛋白结构域3（TIM-3）的表达来增强免疫治疗疗效。总之，miR-545作为一种癌症生物标志物和治疗靶点具有巨大潜力。miR-545在癌症中的异常表达和调控机制值得进一步研究。
