<p>The circ-AMOTL1/ENO1 Axis Implicated in the Tumorigenesis of OLP-Associated Oral Squamous Cell Carcinoma</p>

Abstract

Background: Oral squamous cell carcinoma (OSCC) may develop from a variety of oral potentially malignant disorders, but the mechanism of malignant transformation is still unknown. Among them, oral lichen planus (OLP) has a high prevalence. Previous studies have shown that α-enolase (ENO1) can promote cell proliferation and play an important role in tumorigenesis. In this study, we aim to explore the mechanism of ENO1 regulation in the process of OSCC tumorigenesis from OLP. Methods: ENO1 expression in tissues was determined by real-time quantitative PCR and immunohistochemistry. ENO1 was knocked down in cal-27 to observe the change in cell proliferation. Then, RNA-seq and bioinformatics analyses were conducted between OLP and OSCC samples. The expression of circ-AMOTL1, miRNA-22-3p, and miRNA-1294 was assessed using the real-time quantitative PCR. With knockdown and overexpression of circ-AMOTL1 in vitro, the change of ENO1 in the mRNA level was also assessed. Results: ENO1 was enhanced in the OSCC samples in comparison with OLP. Immunohistochemistry and real-time quantitative PCR results showed that ENO1 was significantly higher in OSCC tissue than in the OLP group, with a statistically significant difference (p<0.05). When ENO1 was knocked down in cal-27, cell proliferation was inhibited (p<0.05). The expression of miR-22-3p and miR-1294 was decreased in OSCC tissues, whereas ENO1 and circ-AMOTL1 increased. In an in vitro study, knockdown of circ-AMOTL1 resulted in a decrease of ENO1, while overexpression of circ-AMOTL1 led to an increase of ENO1 in the mRNA level. Conclusion: We confirmed that ENO1 expression was elevated in OSCC and increased cell proliferation. In an in vitro study, ENO1 expression was promoted by circ-AMOTL1. ENO1 may play a role as a tumor-promoting gene in OSCC through the circ-AMOTL1/miR-22-3p/ miR-1294 network. These novel findings may shed further light on the pathogenesis from OLP to OSCC and the potential precursor markers.

Alpha-Enolase (ENO1) Correlates with Invasiveness of Cutaneous Melanoma—An In Vitro and a Clinical Study

“…The present analysis, performed on patients’ surgical resection specimens, showed that overexpression of ENO1 in tumoral cells was significantly correlated with disease advancement, the presence of metastases in regional lymph nodes, and shorter cancer-specific overall survival. Our clinical observations are in line with previously published clinical research on several other human cancers [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Proteomic analysis of peripheral T-cell lymphomas not otherwise specified (PTCL-NOS) revealed a significantly increased ENO1 level (eightfold) in neoplastic cells compared with the non-lymphoma tissue [ 29 ].…”

ENO1 and Cancer

“…As has been demonstrated by an in vitro study, ENO1 may serve as a tumor-promoting gene in oral squamous cell carcinoma through the circ-AMOTL1/miR-22-3p/miR-1294 network. 77 Similarly, long ncRNA (lncRNA) can also directly bind to ENO1 and regulate its translation. lncRNA P5848 can upregulate both gene and protein expression levels of ENO1, promoting cancer cell growth.…”

Tumor Suppressive Circular RNA-102450: Development of a Novel Diagnostic Procedure for Lymph Node Metastasis from Oral Cancer

“…Oncogenic circRNAs are up-regulated in cancers, promote proliferation, and suppress apoptosis [25][26][27], whereas tumor suppressive circRNAs, as shown for circRNA-102450 in this study, are down-regulated and negatively correlated with cancer progression [28,29]. In OSCC, altered expression of circRNAs has been implicated in carcinogenesis and tumor progression [30,31]; however, the detailed functions and mechanisms of specific circRNAs remain poorly understood.…”