Mei Kun, Chen Zilu, Tan Foxing, Zhou YuHeng, Du Haolin, Gu Renjun, Huang Yan
Nanjing University of Chinese Medicine, Nanjing, China.
Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Discov Oncol. 2025 Apr 1;16(1):445. doi: 10.1007/s12672-025-02223-w.
Esophageal squamous cell carcinoma (ESCC) is a globally prevalent malignancy with high mortality rates. Elucidating the underlying pathophysiological mechanisms of ESCC tumorigenesis is critical for advancing its diagnosis and treatment. MicroRNAs (miRNAs) are pivotal regulators of tumor progression, exerting their effects by binding to target mRNAs and modulating mRNA translation as well as downstream signaling pathways. While the functional roles of numerous miRNAs in ESCC remain incompletely understood, existing studies have implicated autophagy deficiency in aging, cancer, and neurodegenerative diseases. Despite these insights, the relationship between miRNAs and autophagy in ESCC has been insufficiently explored. This study investigates the role of miRNA-221 (miR-221) in ESCC and its interaction with autophagy.
Bioinformatics analysis was employed to determine the biological relevance of miR-221 in ESCC. RT-qPCR was utilized to quantify miR-221 expression in ESCC tissues and cell lines. The effects of miR-221 overexpression or knockdown on cell proliferation and migration were assessed using Cell Counting Kit-8 (CCK8), EdU, and Transwell assays. Western blot analysis was conducted to evaluate autophagy-related changes in ESCC cell lines.
The findings demonstrate that elevated miR-221 expression in tissues from patients with ESCC is a potential independent prognostic marker. Overexpression of miR-221 enhances tumorigenic and metastatic capabilities in ESCC cell lines by suppressing autophagy. Notably, rapamycin-induced autophagy activation partially mitigated the tumor-promoting effects of miR-221 on proliferation and migration.
The interaction between miR-221 and autophagy presents a promising therapeutic target for ESCC management.
食管鳞状细胞癌（ESCC）是一种全球普遍流行且死亡率高的恶性肿瘤。阐明ESCC肿瘤发生的潜在病理生理机制对于推进其诊断和治疗至关重要。微小RNA（miRNA）是肿瘤进展的关键调节因子，通过与靶mRNA结合并调节mRNA翻译以及下游信号通路发挥作用。虽然众多miRNA在ESCC中的功能作用仍未完全了解，但现有研究表明自噬缺陷与衰老、癌症和神经退行性疾病有关。尽管有这些见解，但miRNA与ESCC中自噬之间的关系尚未得到充分探索。本研究调查了miRNA-221（miR-221）在ESCC中的作用及其与自噬的相互作用。
采用生物信息学分析确定miR-221在ESCC中的生物学相关性。利用逆转录定量聚合酶链反应（RT-qPCR）定量ESCC组织和细胞系中miR-221的表达。使用细胞计数试剂盒-8（CCK8）、EdU和Transwell实验评估miR-221过表达或敲低对细胞增殖和迁移的影响。进行蛋白质免疫印迹分析以评估ESCC细胞系中自噬相关的变化。
研究结果表明，ESCC患者组织中miR-221表达升高是一种潜在的独立预后标志物。miR-221的过表达通过抑制自噬增强了ESCC细胞系的致瘤和转移能力。值得注意的是，雷帕霉素诱导的自噬激活部分减轻了miR-221对增殖和迁移的促肿瘤作用。
miR-221与自噬之间的相互作用为ESCC的治疗提供了一个有前景的治疗靶点。
