MicroRNAs and Long Non-Coding RNAs as Regulators of NANOG Expression in the Development of Oral Squamous Cell Carcinoma

Abstract

NANOG is a stem cell transcription factor that is believed to play an important role in the development of oral squamous cell carcinoma (OSCC), but there is limited data regarding the role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the regulation of NANOG expression. We therefore analyzed expression of NANOG, NANOG-regulating miRNAs and lncRNAs in OSCC cancerogenesis, using oral biopsy samples from 66 patients including normal mucosa, dysplasia, and OSCC. Expression analysis of NANOG, miR-34a, miR-145, RoR, SNHG1, AB209630, and TP53 was performed using qPCR and immunohistochemistry for NANOG protein detection. NANOG protein showed no staining in normal mucosa, very weak in low-grade dysplasia, and strong staining in high-grade dysplasia and OSCC. NANOG, miR-145, RoR, and SNHG1 showed up-regulation, TP53 and miR-34a showed down-regulation, and AB209630 showed variable expression during cancerogenesis. NANOG mRNA was up-regulated early in cancerogenesis, before strong protein expression can be detected. NANOG was in correlation with miR-145 and RoR. Our results suggest that miRNAs and lncRNAs, particularly miR-145 and RoR, might be important post-transcription regulatory mechanisms of NANOG in OSCC cancerogenesis. Furthermore, NANOG protein detection has a diagnostic potential for oral high-grade dysplasia, distinguishing it from low-grade dysplasia and non-neoplastic reactive lesions.

Potential Immunohistochemical Biomarkers for Grading Oral Dysplasia: A Literature Review

“…It was noted that expression of NANOG increased with the grade of dysplasia. The importance of NANOG was also confirmed in the study by Grubelnik et al [31], which stated that this marker can be used to differentiate dysplasia grades. NANOG protein detection has a diagnostic potential for oral high-grade dysplasia, distinguishing it from low-grade dysplasia and non-neoplastic reactive lesions.…”

Non-Coding RNAs in Oral Cancer: Emerging Roles and Clinical Applications

“…The miR-21, miR-181b, miR-345, miR-549 and miR-205, were found to be overexpressed both in progressive dysplasia and OC [292]. Another study reported up-regulation of miR-145, lncRNA RoR, and SNHG1 and downregulation of miR-34a from low-grade to high-grade dysplasia and, finally, to OC during carcinogenesis [293]. The lncRNA FGD5-AS1 inhibits NF-kB signaling, and gets downregulated in chronic periodontal samples as compared to the healthy tissues [294].…”