Unraveling Let-7f in oncology: a tumor suppressor with emerging clinical significance

As a major global health threat, tumors present significant clinical challenges due to their heterogeneity, metastatic potential, and therapy resistance. In recent years, non-coding RNAs, particularly microRNAs (miRNAs), have emerged as crucial players in cancer research. Among them, let-7f, a key member of the let-7 family, exhibits significant dysregulation and biological functions in various cancers. This review systematically summarizes the differential expression patterns of let-7f in common malignancies, revealing its prevalent downregulation in cancers such as lung, gastric, colorectal, breast, and glioblastoma. This downregulation is closely associated with tumor size, stage, metastatic potential, and patient prognosis. The expression of let-7f is regulated by multiple molecular mechanisms, including transcription factors (e.g., C/EBPβ), RNA-binding proteins (e.g., LIN28), ceRNA networks (e.g., FAM222A-AS1, LINC00106), and genetic polymorphisms. Regarding biological functions, let-7f inhibits tumor cell proliferation, invasion, metastasis, stemness maintenance, and metabolic reprogramming by targeting multiple oncogenes (e.g., MYH9, HMGA2, ADAMTS1, Periostin) and key signaling pathways (e.g., MAPK, Wnt, PI3K/AKT). Furthermore, let-7f is involved in modulating the tumor microenvironment, including angiogenesis, stromal cell function, and the immune milieu. At the therapeutic level, let-7f not only serves as a predictive biomarker for the efficacy of chemotherapy, radiotherapy, and endocrine therapy but also holds potential for reversing drug resistance and enhancing drug sensitivity. For diagnosis, its stable presence in body fluids like plasma and stool offers a non-invasive detection advantage, positioning it as a promising novel biomarker for various cancers. However, challenges remain, including the standardization of detection methods, optimization of delivery systems, and insufficient clinical validation. Future efforts should integrate multi-omics analyses, artificial intelligence-assisted modeling, and novel nanodelivery technologies to advance the translation of let-7f from basic research to clinical application, thereby providing new strategies for the precise diagnosis and treatment of cancer.