AAAGUGC Seed-Containing miRNAs: Master Regulators of Cancer Pathways and Therapeutic Resistance.

Chandhru Srinivasan, Mano Chitra Karthikeyan, Abirami Jeyaprakash, Antony Joseph Velanganni Arockiam
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Abstract

MicroRNAs have emerged as pivotal post-transcriptional regulators, orchestrating a myriad of cellular processes critical to both normal physiology and pathological conditions, par-ticularly cancer. Among these, miRNAs containing the highly conserved AAAGUGC seed se-quence have garnered significant attention due to their multifaceted roles in cancer progression, acting as both oncogenes and tumour suppressors across a wide spectrum of malignancies. This review delves deeply into the evolutionary significance of AAAGUGC seed-containing miRNAs, elucidating their conserved nature and intricate roles in the regulation of cancer-related gene ex-pression networks. We focused on eight specific miRNAs- miR-17-5p, miR-20a-5p, miR-93-5p, miR-106a-5p, miR-106b-5p, miR-519d-3p, miR-526b-3p, and miR-20b-5p -each of which demonstrates con-text-dependent oncogenic or tumour-suppressive behaviour. Through an in-depth exploration of the molecular mechanisms by which these miRNAs modulate critical pathways, we highlighted their capacity to influence essential processes, including cell proliferation, apoptosis, epithelial-to-mesenchymal transition (EMT), metastasis, and drug resistance, reflecting the complexity of their regulatory roles. Furthermore, we dissected the intricate interactions between these miRNAs and their downstream targets, showcasing their diverse contributions to the tumour microenvironment. The implications of miRNA dysregulation in chemotherapy resistance were also explored. In conclusion, AAAGUGC seed-containing miRNAs represent a complex and evolutionarily conserved family with implications in cancer biology. Their ability to modulate multiple onco-genic and tumour-suppressive pathways highlights their potential as therapeutic targets or bi-omarkers in the context of personalized cancer treatment strategies. This review provides a com-prehensive depth of current knowledge while proposing avenues for future research into the ther-apeutic manipulation of these miRNAs in combating cancer.

含有AAAGUGC种子的miRNAs:癌症途径和治疗耐药性的主要调控因子。
microrna已成为关键的转录后调节因子,调控着对正常生理和病理状况(尤其是癌症)至关重要的无数细胞过程。其中,含有高度保守的AAAGUGC种子序列的mirna由于其在癌症进展中的多方面作用而引起了极大的关注,在广泛的恶性肿瘤中充当致癌基因和肿瘤抑制因子。这篇综述深入探讨了含有AAAGUGC种子的mirna的进化意义,阐明了它们的保守性和在癌症相关基因表达网络调控中的复杂作用。我们重点研究了8种特定的mirna - miR-17-5p, miR-20a-5p, miR-93-5p, miR-106a-5p, miR-106b-5p, miR-519d-3p, miR-526b-3p和miR-20b-5p -每一种都表现出上下文依赖的致癌或肿瘤抑制行为。通过深入探索这些mirna调节关键通路的分子机制,我们强调了它们影响细胞增殖、凋亡、上皮-间质转化(EMT)、转移和耐药性等基本过程的能力,反映了它们调节作用的复杂性。此外,我们剖析了这些mirna与其下游靶标之间复杂的相互作用,展示了它们对肿瘤微环境的不同贡献。我们还探讨了miRNA失调在化疗耐药中的意义。总之,含有AAAGUGC种子的mirna代表了一个复杂的、进化保守的家族,在癌症生物学中具有重要意义。它们调节多种致癌和肿瘤抑制途径的能力突出了它们在个性化癌症治疗策略中作为治疗靶点或双标记物的潜力。这篇综述提供了当前知识的全面深度,同时为未来研究这些mirna在抗癌中的治疗性操作提出了途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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