Oral squamous cell carcinoma (OSCC) represents the most prevalent form of head and neck cancer, accounting for over 90 % of oral malignancies, and is characterized by aggressive progression, frequent lymph node metastasis, and poor prognosis (Chamoli et al., 2021; Vitorio et al., 2020). Although there have been advancements in many anti-cancer therapies, the five-year survival rate for OSCC remains low, largely due to a late-stage diagnosis and limited understanding of the molecular mechanisms driving tumorigenesis and metastasis (Kitamura et al., 2020; Mei et al., 2020). Tumor angiogenesis, a hallmark of cancer progression, is pivotal in OSCC progression as it supplies nutrients and oxygen to rapidly proliferating tumor cells (Li et al., 2023). The development of OSCC is a complex biological process involving genetic alterations, epigenetic modifications, and dysregulated tumor microenvironment (Cai et al., 2024; Calanca et al., 2023). The identification of relevant biomarkers can facilitate the exploration of effective targets for oral carcinogenesis. Therefore, it is imperative to understand the biology of OSCC and to explore its diagnostic and therapeutic targets.

MicroRNAs (miRNAs) have been demonstrated to exert pivotal regulatory roles in a multitude of physiological processes, including growth and development, proliferation, migration, and angiogenesis (Kumar & Anjali, 2022; Tong et al., 2022). They are indispensable in maintaining cellular functions and homeostasis in organisms. Numerous studies have identified potential cancer biomarkers, especially miRNAs, for diagnostic and prognostic applications, thereby paving the way for novel cancer screening methods (Yaghoubi et al., 2022). This field of research holds considerable potential for enhancing our understanding of cancer biology and developing new therapeutic strategies. The miR-34 family, a group of tumor-suppressive miRNAs, has been implicated in the modulation of biological processes such as growth, apoptosis, and metastasis across various cancers (Sun et al., 2021; Welponer et al., 2020). Notably, miR-34b-3p, a member of this family, has shown dysregulated expression in multiple malignancies, including cervical and non-small cell lung cancers (Feng et al., 2019; Jin et al., 2024). However, its functional role and mechanistic contributions to OSCC pathogenesis, particularly in tumor angiogenesis, remain poorly explored. Sex Determining Region Y-box protein 5 (SOX5), a transcription factor involved in developmental processes and oncogenic signaling, has been linked to tumor progression in several cancers (Sun et al., 2019; Wu et al., 2022). Preliminary bioinformatics analyses have suggested a potential interaction between miR-34b-3p and SOX5; however, this axis has not been experimentally validated in OSCC.

Our research aimed to ascertain the clinical relevance of miR-34b-3p in OSCC prognosis and its regulatory effects on tumor angiogenesis. We hypothesized that miR-34b-3p acts as a tumor inhibitor by regulating SOX5, thereby inhibiting tumor angiogenesis and OSCC progression. Through a combination of clinical analyses, in vitro functional assays, and mechanistic studies, we elucidated the diagnostic and prognostic potential of miR-34b-3p in patients with OSCC and demonstrated its functions in modulating cellular behaviors and angiogenesis via SOX5.