关键词: Biomarker Cell behavior Competing endogenous RNA Immunotherapy Therapeutic drug miR-545

来  源:   DOI:10.1016/j.cpt.2023.09.001   PDF(Pubmed)

Abstract:
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) FTX 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.
摘要:
微核糖核酸(miRNA)是一类高度保守的单链非编码RNA。在miR-545/374a簇内,miR-545位于Xq13.2上的长链非编码RNA(lncRNA)FTX的内含子中。前体形式,pre-miR-545被切割以产生两个成熟的miRNA,miR-545-3p和miR-545-5p。值得注意的是,这两种miRNA在不同的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个环状RNA(circRNAs)和10个长链非编码RNA(lncRNAs)的影响,它靶向27个蛋白质编码基因(PCGs),参与4个信号通路的调节。相比之下,miR-545-5p受一个circRNA和五个lncRNAs调控,它靶向六个PCGs,并有助于一个信号通路的调节。miR-545-3p和miR-545-5p都影响关键的细胞行为,包括细胞周期,扩散,凋亡,上皮-间质转化,入侵,和移民。尽管低miR-545-3p表达与三种癌症类型的不良预后相关,关于miR-545-5p的研究尚未报道。miR-545-3p在多种调控网络中运作,从而增强癌症化疗的疗效,放射治疗,和免疫疗法。相反,miR-545-5p通过抑制T细胞免疫球蛋白和含粘蛋白结构域3(TIM-3)表达来增强免疫疗法功效。总之,miR-545作为癌症生物标志物和治疗靶标具有巨大潜力。miR-545在癌症中的异常表达和调控机制需要进一步研究。
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