Xia Qing, Liu Guanghua, Lin Wenbo, Zhang Jin
Department of General Surgery, Hwa Mei Hospital (Ningbo No.2 Hospital), University of Chinese Academy of Sciences, Ningbo, China.
Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China.
Mol Carcinog. 2025 Jan;64(1):33-43. doi: 10.1002/mc.23824. Epub 2024 Oct 14.
Cancer stem cells (CSCs) are involved in the regulation of tumor initiation, progression, recurrence, and chemoresistance. However, the role of microRNAs (miRNAs) in liver CSCs has not been fully understood. Here we show that miR-2117 is downregulated in liver CSCs and predicts the poor prognosis of hepatocellular carcinoma (HCC) patients. Biofunction studies found that knockdown miR-2117 facilitates liver CSCs self-renewal and tumorigenesis. Conversely, forced miR-2117 expression suppresses liver CSCs self-renewal and tumorigenesis. Mechanistically, we find that transcription factor SOX2 is required for miR-2117-mediated liver CSCs expansion. The correlation between miR-2117 and SOX2 was confirmed in human HCC tissues. More importantly, miR-2117 overexpression HCC cells are more sensitive to CDDP treatment. Analysis of patients' cohort further demonstrates that miR-2117 may predict transcatheter arterial chemoembolization benefits in HCC patients. Our findings revealed the crucial role of miR-2117 in liver CSCs expansion, rendering miR-2117 as an optimal therapeutic target for HCC.
癌症干细胞(CSCs)参与肿瘤的起始、进展、复发及化疗耐药的调控。然而,微小RNA(miRNAs)在肝脏CSCs中的作用尚未完全明确。在此我们发现,miR-2117在肝脏CSCs中表达下调,并可预测肝细胞癌(HCC)患者的不良预后。生物学功能研究发现,敲低miR-2117可促进肝脏CSCs的自我更新及肿瘤发生。相反,强制表达miR-2117则抑制肝脏CSCs的自我更新及肿瘤发生。机制上,我们发现转录因子SOX2是miR-2117介导的肝脏CSCs扩增所必需的。miR-2117与SOX2之间的相关性在人类HCC组织中得到证实。更重要的是,过表达miR-2117的HCC细胞对顺铂治疗更敏感。对患者队列的分析进一步表明,miR-2117可能预测HCC患者经动脉化疗栓塞术的疗效。我们的研究结果揭示了miR-2117在肝脏CSCs扩增中的关键作用,使miR-2117成为HCC的一个最佳治疗靶点。