MicroRNA miR-122 plays a pivotal role in liver function. Despite numerous studies investigating this miRNA, the global network of genes regulated by miR-122 and its contribution to the underlying pathophysiological mechanisms remain largely unknown. To gain a deeper understanding of miR-122 activity, we employed two complementary approaches. Firstly, through transcriptome analysis of polyribosome-bound RNAs, we discovered that miR-122 exhibits potential antagonistic effects on specific transcription factors known to be dysregulated in liver disease, including nuclear respiratory factor-1 (NRF1) and the E2F transcription factor 4 (E2F4). Secondly, through proteome analysis of hepatoma cells transfected with either miR-122 mimic or antagomir, we discovered changes in several proteins associated with increased malignancy. Interestingly, many of these proteins were reported to be transcriptionally regulated by NRF1 and E2F4, six of which we validated as miR-122 targets. Among these, a negative correlation was observed between miR-122 and glucose-6-phosphate dehydrogenase levels in the livers of patients with hepatitis B virus-associated hepatocellular carcinoma. This study provides novel insights into potential alterations of molecular pathway occurring at the early stages of liver disease, driven by the dysregulation of miR-122 and its associated genes.
MicroRNA miR-122在肝脏功能中发挥着关键作用。尽管已有大量研究探讨该miRNA，但miR-122调控的全局基因网络及其在相关病理生理机制中的作用仍不甚明确。为深入理解miR-122的生物学功能，我们采用两种互补的研究策略：首先通过多聚核糖体结合RNA的转录组分析，发现miR-122对特定转录因子可能具有拮抗作用，这些因子包括核呼吸因子-1（NRF1）和E2F转录因子4（E2F4），且已知它们在肝脏疾病中表达失调；其次通过转染miR-122模拟物或抑制剂的肝癌细胞蛋白质组分析，发现多个与恶性程度增强相关的蛋白表达发生变化。值得注意的是，这些蛋白中有许多已被报道受NRF1和E2F4的转录调控，其中六种经我们验证确为miR-122的靶标。特别在乙型肝炎病毒相关肝细胞癌患者肝脏组织中，我们观察到miR-122与葡萄糖-6-磷酸脱氢酶水平呈负相关。本研究为揭示miR-122及其相关基因失调驱动的肝脏疾病早期分子通路改变提供了新的见解。
肿瘤(癌症)患者之家