Tongue squamous cell carcinoma (TSCC) is an aggressive oral malignancy with an increasing incidence worldwide, however, the molecular regulatory mechanisms underlying its progression still unclear. Existing studies demonstrate that microRNAs (miRNAs) play a critical role in TSCC progression. In particular, the regulatory relationship between the oncogenic miR-21-5p and the tumor suppressor gene FDX1, as well as its targeted effect on the natural compound AT-101, remains a clear research gap. In this study, CTD, dbMEMC, and TCGA databases were used to screen AT-101-related genes and the miR-21-5p/FDX1 regulatory axis, the expression patterns of which were validated in TSCC tissues and cell lines (HaCaT, HSC3, Cal27) using RT-qPCR and Western blot. Functional assays (cell proliferation, Transwell, wound healing) demonstrated that miR-21-5p promotes TSCC proliferation, migration, and invasion, and dual-luciferase reporter assays further confirmed FDX1 as its direct target. Additionally, AT-101 significantly down-regulated miR-21-5p, restored FDX1 expression, and suppressed TSCC cell growth. Mechanistic studies revealed that miR-21-5p drives TSCC progression by suppressing FDX1, while AT-101 reverses this effect by restoring FDX1 levels and modulating critical signaling pathways to inhibit tumor development. Collectively, the miR-21-5p/FDX1 axis plays a crucial regulatory role in TSCC, and AT-101 can inhibit the malignant phenotype of TSCC by interfering with this axis. This study uncovers the underlying molecular mechanisms of TSCC and provides novel strategies for its targeted therapy.
Fu et al. (Tue,) studied this question.