Cai Jiajia, Yan Zeqin, Zhong Yadi, Li Yuqing, Huang Jianxu, Hu Huijuan, Li Yingrui, Fang Hu, Wu Song
Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China.
Department of Urology, The Affiliated Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, Shenzhen, 518009, China.
BMC Cancer. 2025 Feb 21;25(1):319. doi: 10.1186/s12885-025-13672-5.
The intricate regulatory roles of small non-coding RNAs (sncRNAs), including PIWI-interacting RNAs (piRNAs) and microRNAs (miRNAs), have been increasingly recognized in the modulation of cellular functions and are associated with the pathogenesis of various diseases, notably cancer. However, the specific dysregulation patterns of sncRNAs in non-muscle-invasive bladder cancer (NMIBC) have yet to be fully delineated, highlighting a significant gap in our current understanding. To elucidate the expressional dynamics of sncRNAs for patients with NMIBC, we characterized the profile of piRNAs and miRNAs by next-generation sequencing. We identified the differentially expressed sncRNAs between tumor and paracancerous tissues and characterized their distribution along the genome. We further revealed a set of immune-related piRNAs and dysregulated miRNAs that might be associated with NMIBC pathogenesis. Differentially expressed piRNAs were predominantly localized at the long arms of chromosomes 13, 1, and 6. Notably, the targets of specific piRNAs, including piR-hsa-2215234, piR-hsa-105306, piR-hsa-102066, and piR-hsa-236465, show significant associated with antigen processing and presentation pathway. Additionally, differentially expressed miRNAs are mainly located on chromosome 14 and their target genes tend to be involved in cancer-related pathways, suggesting their potential regulatory roles in NMIBC. Collectively, this study revealed the global sncRNA dysregulation in NMIBC, and the identified sncRNAs are implicated in the modulation of both immune and cancer pathways, suggesting their contribution to the pathogenesis and potential targets for immunotherapy.
包括PIWI相互作用RNA(piRNA)和微小RNA(miRNA)在内的小非编码RNA(sncRNA)的复杂调控作用在细胞功能调节中得到了越来越多的认识,并且与包括癌症在内的各种疾病的发病机制相关。然而,非肌层浸润性膀胱癌(NMIBC)中sncRNA的具体失调模式尚未完全阐明,这凸显了我们目前理解上的重大差距。为了阐明NMIBC患者sncRNA的表达动态,我们通过下一代测序对piRNA和miRNA的谱进行了表征。我们鉴定了肿瘤组织和癌旁组织之间差异表达的sncRNA,并表征了它们在基因组中的分布。我们进一步揭示了一组可能与NMIBC发病机制相关的免疫相关piRNA和失调的miRNA。差异表达的piRNA主要定位于13号、1号和6号染色体的长臂。值得注意的是,特定piRNA的靶标,包括piR-hsa-2215234、piR-hsa-105306、piR-hsa-102066和piR-hsa-236465,显示出与抗原加工和呈递途径有显著关联。此外,差异表达的miRNA主要位于14号染色体上,其靶基因倾向于参与癌症相关途径,表明它们在NMIBC中具有潜在的调控作用。总体而言,本研究揭示了NMIBC中整体sncRNA失调,并且鉴定出的sncRNA参与了免疫和癌症途径的调节作用,表明它们对发病机制的贡献以及作为免疫治疗的潜在靶点。