Expression of NOTCH1 Is Correlated with Expression of Cancer Stem Cell Markers and miR-150 in Oral Epithelial Dysplasia

NOTCH1 is associated with various tumors, including oral squamous cell carcinoma (OSCC), with a complex role depending on cellular contexts. Our aim was to analyze the expression of NOTCH1, several stem cell markers, and selected microRNAs in preneoplastic lesion of the oral cavity, oral epithelial dysplasia (OAD). Our study included formalin-fixed paraffin-embedded biopsy samples of 36 cases of OAD and 15 cases of normal oral mucosa. Expression of <i>NOTCH1</i>, stem cell markers (<i>AGR2</i>, <i>KLF4</i>, <i>NANOG</i>, <i>OCT4</i>, <i>SOX2</i>), and <i>miR-27a</i>, <i>miR-34a</i>, <i>miR-128</i>, <i>miR-145</i>, <i>miR-150</i>, and <i>miR-335</i> was analyzed by quantitative PCR (qPCR). Expression of NOTCH1 protein was analyzed by immunohistochemistry. In OAD compared to normal mucosa, we found a significant increase in mRNA levels of <i>NOTCH1</i>, stem cell markers <i>AGR2</i>, <i>NANOG</i>, <i>OCT4</i>, and <i>SOX2</i>, and <i>miR-150</i> and <i>miR-128</i>. <i>NOTCH1</i> mRNA positively correlated with all five stem cell markers' mRNA levels and <i>miR-150</i>. Immunohistochemistry showed variable expression patterns of NOTCH1 in OAD and normal mucosa. Our results support the role of NOTCH1 in early phases of OSCC development, with a potential contributory role in stemness, in association with <i>AGR2</i>, <i>NANOG</i>, <i>OCT4</i>, and <i>SOX2</i>, <i>miR-150</i> and <i>miR-128</i>. These results support a complex role of NOTCH1 in carcinoma development, i.e., from oncogenic to tumor suppressor roles and stemness maintenance, not only in invasive OSCC but also in its precursor-OED.