International Journal of Molecular Medical Science, 2025, Vol.15, No.1, 9-19 http://medscipublisher.com/index.php/ijmms 13 Epigenetic changes, including DNA methylation and histone modifications, are crucial in OSCC pathogenesis. Aberrant methylation patterns, such as hypermethylation of tumor suppressor genes like CDKN2A, contribute to silencing these genes and promote uncontrolled cell proliferation. Epigenetic alterations can also modulate gene expression through changes in chromatin structure, affecting the transcription of genes involved in differentiation and apoptosis (Zhang et al., 2015). Understanding these changes is critical for developing targeted therapies that can reverse epigenetic silencing and restore normal gene function in OSCC. 4.2 MicroRNA dysregulation in tumorigenesis MicroRNAs (miRNAs) are small non-coding RNAs that play a pivotal role in gene regulation, and their dysregulation is a hallmark of many cancers, including OSCC. In OSCC, specific miRNAs function as oncogenes or tumor suppressors, impacting various processes like proliferation, apoptosis, and metastasis. For instance, downregulation of the miR-200 family is associated with the promotion of Epithelial-To-Mesenchymal Transition (EMT), which enhances the invasive potential of cancer cells (Arunkumar et al., 2017). Other miRNAs, such as miR-21 and miR-375, have been identified as potential biomarkers for OSCC diagnosis due to their consistent expression patterns in cancer tissues and body fluids (He et al., 2016). The overexpression of miR-21, for example, is known to target and suppress tumor suppressor genes like PTEN, leading to enhanced cell survival and resistance to apoptosis. Conversely, restoration of tumor-suppressive miRNAs, such as miR-16, has been shown to inhibit OSCC cell proliferation and induce apoptosis by targeting oncogenic pathways. These findings highlight the therapeutic potential of miRNAs as both biomarkers and targets in OSCC treatment. 4.3 Protein expression and tumorigenesis Alterations in protein expression are crucial in the progression of OSCC, as they reflect changes in cellular signaling pathways that drive tumorigenic processes. Overexpression of proteins like S100A9 and Caveolin-1 has been associated with increased invasiveness and poor prognosis in OSCC patients (Fang et al., 2015), (Auzair et al., 2016). S100A9, for example, can promote tumor cell invasion by interacting with the tumor microenvironment and inducing pro-inflammatory cytokine production, which supports tumor growth. The transcription factor Yes-Associated Protein (YAP), a key component of the Hippo signaling pathway, plays an essential role in regulating cell proliferation and apoptosis in OSCC. Figure 1A demonstrates strong YAP expression in well-differentiated OSCC, while Figure 1B shows similar overexpression in moderately differentiated OSCC. The strong immunohistochemical staining indicates that YAP is highly active in both OSCC types, and its elevated expression has been correlated with increased tumor aggressiveness and poor patient outcomes (Figure 1) (Shelke et al., 2019). This highlights YAP's involvement in driving OSCC progression, making it a potential therapeutic target. Figure 1 A and B: Photomicrograph showing strong expression of YAP in different grades of OSCC (Adapted from Shelke et al., 2019) Image caption: (A) Well-differentiated OSCC; (b) Moderately differentiated OSCC (total magnification×400; IHC staining).The strong expression of YAP in both well-differentiated and moderately differentiated OSCC tissues suggests that YAP may play a role in the progression of OSCC, regardless of differentiation grade. This highlights the potential of YAP as a biomarker for OSCC, and possibly a therapeutic target, since its activity may be associated with cancer cell proliferation and survival (Adapted from Shelke et al., 2019)
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