Rathore Deepshikha, Jain Sweny, Patel Shanaya, Dharwal Nandani, Shukla Nirali, Desai Chirag, Shah Jigna, Dave Heena V
Institute of Science, Nirma University, Ahmedabad, Gujarat, India.
Division of Biological & Life Sciences, School of Arts & Sciences, Ahmedabad University, Ahmedabad, Gujarat, India.
Med Oncol. 2025 Jun 28;42(8):296. doi: 10.1007/s12032-025-02846-7.
MicroRNAs or miRNAs are characterized as non-coding RNAs, and these are the critical regulators of gene expression post-transcription. Emerging evidence highlights their important role in both the progression and repression of cancer. miRNAs, found in both primary tumor cells and circulation, not only regulate primary tumor development but also regulate metastatic progression by affecting the behavior of primary tumor cells and resident cells at distant organs. Metastasis remains a major clinical challenge in cancer treatment, which limits the therapeutic efficacy and reduces patient survival significantly. This challenge is particularly evident in triple-negative breast cancers (TNBC). This malignancy responds poorly to current chemotherapies and lacks reliable biomarkers, thus, it lacks targeted therapy options. Notably, TNBC exhibits a high propensity for metastasis to critical organs such as the brain, bone, liver, and lung. The process of metastasis of TNBC primary tumor remains unclear, which highlights the critical need to uncover its molecular insights and organ-specific biomarkers. As key regulators of metastasis, microRNAs play a vital role in TNBC progression by modulating gene expression in primary tumor cells and functioning as circulating messenger molecules that affect distant metastatic sites. Furthermore, their potential as therapeutic targets are currently being explored in preclinical models, including the development of anti-miRNA oligonucleotides and miRNA mimics. Overall, this review offers an in-depth mechanism of TNBC metastasis and the molecular mechanisms driving the brain, bone, liver, and lung metastasis. The key focus is on understanding the role of miRNAs in directing organ-specific metastasis and evaluating their potential as biomarker for diagnosis and targeted treatment.
微小RNA（miRNA）被定义为非编码RNA，是转录后基因表达的关键调节因子。新出现的证据凸显了它们在癌症进展和抑制过程中的重要作用。在原发性肿瘤细胞和循环系统中均发现的miRNA，不仅调节原发性肿瘤的发展，还通过影响原发性肿瘤细胞和远处器官驻留细胞的行为来调节转移进程。转移仍然是癌症治疗中的一项主要临床挑战，它限制了治疗效果并显著降低了患者生存率。这一挑战在三阴性乳腺癌（TNBC）中尤为明显。这种恶性肿瘤对当前化疗反应不佳且缺乏可靠的生物标志物，因此缺乏靶向治疗选择。值得注意的是，TNBC极易转移至脑、骨、肝和肺等关键器官。TNBC原发性肿瘤的转移过程尚不清楚，这凸显了揭示其分子机制和器官特异性生物标志物的迫切需求。作为转移的关键调节因子，miRNA通过调节原发性肿瘤细胞中的基因表达以及作为影响远处转移部位的循环信使分子，在TNBC进展中发挥着至关重要的作用。此外，目前正在临床前模型中探索它们作为治疗靶点的潜力，包括抗miRNA寡核苷酸和miRNA模拟物的开发。总体而言，本综述深入探讨了TNBC转移的机制以及驱动脑、骨、肝和肺转移的分子机制。重点在于了解miRNA在指导器官特异性转移中的作用，并评估它们作为诊断和靶向治疗生物标志物的潜力。
