铁死亡（ferroptosis）是一种依赖铁离子的细胞死亡形式，而失调的微小核糖核酸（microRNA，miRNA）表达与结直肠癌（colorectal cancer，CRC）的发展和进展相关。miR-148a-3p的肿瘤抑制能力已在多种癌症中被报道。然而，miR-148a-3p在CRC中的作用仍然未完全确定。在本研究中，我们旨在调查miR-148a-3p在CRC细胞死亡机制中的分子机制和调节靶点。为此，我们利用定量实时聚合酶链反应（qRT-PCR）评估了SW480和SW620细胞以及正常结肠上皮CCD 841 CoN细胞中的miR-148a-3p表达。数据显示，与非肿瘤细胞相比，SW480和SW620细胞的miR-148a-3p表达下降（p < 0.05）。miR-148a的过表达选择性地抑制了CRC细胞的存活能力（p < 0.001），而对正常CCD 841 CoN细胞的存活影响较小（p < 0.05）。在细胞水平上，miR-148a-3p模拟物通过激活半胱氨酸天冬酶（caspase-3）（p < 0.001），增加线粒体活性氧（ROS）积累（p < 0.001）和膜去极化（p < 0.001）促进凋亡性细胞死亡。此外，miR-148a-3p的过表达诱导了脂质过氧化（p < 0.01），GPX4的下调（p < 0.01）和铁死亡（p < 0.01），如细胞内和线粒体内的铁离子积累以及ACSL4/TFRC/Ferritin的调节所示。另外，通过生物信息学工具预测，miR-148a-3p过表达抑制了SLC7A11 mRNA和蛋白质的水平，这些是miR-148a-3p的细胞靶点。相反，miR-148a-3p的下调增加了SLC7A11基因的表达并抑制了铁死亡。综上所述，这些体外发现揭示了miR-148a-3p通过靶向SLC7A11并激活铁死亡作为CRC的肿瘤抑制因子的功能，为通过靶向miR-148a-3p/SLC7A11途径进行治疗策略提供了新的视角。

Ferroptosis, an iron-dependent form of cell death, and dysregulated microRNA (miRNA) expression correlate with colorectal cancer (CRC) development and progression. The tumor suppressor ability of miR-148a-3p has been reported for several cancers. Nevertheless, the role of miR-148a-3p in CRC remains largely undetermined. Here, we aim at investigating the molecular mechanisms and regulatory targets of miR-148a-3p in the CRC cell death mechanism(s). To this end, miR-148a-3p expression was evaluated in SW480 and SW620 cells and normal colon epithelial CCD 841 CoN cells with quantitative real-time polymerase chain reaction (qRT-PCR). Data reported a reduction of miR-148a-3p expression in SW480 and SW620 cells compared to non-tumor cells (p < 0.05). Overexpression of miR-148a selectively inhibited CRC cell viability (p < 0.001), while weakly affecting normal CCD 841 CoN cell survival (p < 0.05). At the cellular level, miR-148a-3p mimics promoted apoptotic cell death via caspase-3 activation (p < 0.001), accumulation of mitochondrial reactive oxygen species (ROS) (p < 0.001), and membrane depolarization (p < 0.001). Moreover, miR-148a-3p overexpression induced lipid peroxidation (p < 0.01), GPX4 downregulation (p < 0.01), and ferroptosis (p < 0.01), as revealed by intracellular and mitochondrial iron accumulation and ACSL4/TFRC/Ferritin modulation. In addition, levels of SLC7A11 mRNA and protein, the cellular targets of miR-148a-3p predicted by bioinformatic tools, were suppressed by miR-148a-3p's overexpression. On the contrary, the downregulation of miR-148a-3p boosted SLC7A11 gene expression and suppressed ferroptosis. Together, these in vitro findings reveal that miR-148a-3p can function as a tumor suppressor in CRC by targeting SLC7A11 and activating ferroptosis, opening new perspectives for the rationale of therapeutic strategies through targeting the miR-148a-3p/SLC7A11 pathway.