Head and neck cancers (HNC) are a wide group of tumors arising from the mucosa of the upper aerodigestive tract, including the salivary glands, oral cavity, nasopharynx, oropharynx, hypopharynx and larynx (Sanli and Karatas, 2023). Head and neck carcinoma is the sixth most common cancer worldwide, with approximately 650,000 annual new cases and over 300,000 deaths per year (Picon and Guddati, 2020). Due to the lack of successful diagnostic markers, approximately two-thirds of patients are usually diagnosed at an advanced stage or with distant metastasis (Budach and Tinhofer, 2019). The overall survival rate of late-stage HNC patients is remarkably low (Bhat et al., 2021). Given the complex anatomy and critical patho-physiological impacts of the tumor tissues on this region, the goal of treatment is not only to increase the survival of patients, but also to protect the functionality of organs (Ackerman et al., 2018).

The treatment method to be used varies depending on the stage of the tumor, pathology, anatomical site and surgical accessibility (Chow, 2020). Surgery, radiotherapy and chemotherapy are the most commonly used therapeutic modalities for HNC patients (Aytatli et al., 2022). On the other hand, chemotherapy, rather than surgery or radiotherapy, is the main form of treatment for post-operative or advanced HNCs, decreasing post-operative recurrence, prolonging survival, and enhancing the quality of life. (Bhide and Nutting, 2010).

Paclitaxel, also known as taxol, is an important anti-mitotic chemotherapeutic agent that belongs to the taxane family (Yang et al., 2020; Yu et al., 2022). Taxol binds to the β-subunit of microtubules and leads to mitotic arrest, cell division inhibition and cell death through stabilization of microtubules (Alqahtani et al., 2019; Orr et al., 2003). Although taxol has been effectively used to treat various cancers including HNCs (Aytatli et al., 2022), development of resistance to chemotherapeutic agents significantly limits therapeutic efficacy and may give rise to failure of treatment in HNCs (Bier, 1993; Iida et al., 2022; Roh et al., 2017). Therefore, it is important to elucidate the mechanisms leading to chemoresistance, which in turn may lead to the development of new therapeutic strategies to overcome drug resistance in HNC patients.

MicroRNAs are single-stranded, approximately 19–25 nucleotides long, endogenously synthesized short RNA molecules that participate in both post-transcriptional and translational regulation of target mRNAs (Meng et al., 2020a; Zhang et al., 2019). MicroRNAs have been shown to be essential drivers of various pathological processes associated with malignancies, including HNCs (Chakraborty et al., 2016; Sun et al., 2013) and reported to be involved in therapeutic response of tumor moieties by regulating target genes expressions (Pan et al., 2021; Sun et al., 2016). An increasing quantity of research suggests that many microRNAs contribute to the regulation of chemotherapy resistance, notably in HNCs (Liu et al., 2013; Wang et al., 2017; Zhao et al., 2020). Therefore, functional characterization of these microRNAs and their downstream targets could be potentially advantageous for development of new therapeutic approaches. MiR-200c-3p is a significant member of the miR-200 family, which also contains miR-200a, miR-200b, miR-200c, miR-141 and miR-429 (Meng et al., 2020b). Various studies have been demonstrated that miR-200c-3p is frequently downregulated and has a tumor suppressor potential in many cancers. For example, miR-200c suppressed tumor metastasis and angiogenesis by downregulating HIF-1α in human lung cancer cells (Byun et al., 2019). Lo et al. reported that upregulation of miR-200c attenuates the tumor growth and stemness properties of HNC cells (Lo et al., 2011). In addition, Ting et al. demonstrated that miR-200c-3p suppresses proliferation, migration and invasion of nephroblastoma cells by decreasing FRS2 expression (Li et al., 2019). Interestingly, previous investigations revealed that miR-200c-3p might increase the anti-cancer actions of chemotherapy drugs in a variety of malignancies. Vescarelli et al. demonstrated that miR-200c significantly increased the anti-cancer efficacy of olaparib on ovarian cancer cells by directly targeting NRP1 (Vescarelli et al., 2020). Furthermore, Huang et al. demonstrated that miR-200c-3p inhibits the malignant phenotype of non-small cell lung cancer cells by targeting RRM2 and promotes cisplatin sensitivity (Liu et al., 2022). However, the roles of miR-200c-3p still remain unclear during acquisition of resistance against taxol in HNCs. Therefore, further studies are needed to better understand the roles of miR-200c-3p and its targets and to evaluate their interactions with oncogenes in the processes leading to taxol resistance in HNCs.

Overall, in the present study, we examined the role of miR-200c-3p in HNC progression and taxol resistance via a series of experiments. We revealed that the expression of miR-200c-3p was downregulated in HNC tissues, HNC cells in addition to taxol-resistant HNC cells. Furthermore, we identified Sperm-specific antigen 2 (SSFA2) as a direct target of miR-200c-3p and further evaluated its roles in HNC progression and taxol resistance. We suggest that a better understanding of the role of miR-200c-3p/SSFA2 axis in HNC progression may be a promising strategy to eliminate taxol resistance in HNCs.