RESUMEN
The abnormal expression of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) is closely related to several tumor diagnosis and progression, such as endometrial carcinoma and ovarian cancer. However, the role of MEG3 in oral squamous cell carcinoma (OSCC) is rarely reported. The current study aimed to evaluate the expression of lncRNA MEG3 in OSCC tissues and cell lines and its effect on the biological behavior of OSCC cell lines. The expression of lncRNA MEG3 in the OSCC tissues and cell lines was detected by reverse transcription-quantitative (RT-q) PCR. The relationship between MEG3 expression and the clinicopathologic characteristics and prognosis of patients with OSCC was analyzed. The lncRNA MEG3 overexpression plasmid and control plasmid were transfected into SCC25 and CAL27 cell lines using the lipofectin method. MTT assay was performed to detect the growth and proliferation of the cell lines. Transwell chamber test was used to detect changes in cell migration and invasion. Flow cytometry was employed to detect changes in apoptosis. Western blotting and RT-qPCR were conducted to detect the expression of the p53 gene. The expression of lncRNA MEG3 in the OSCC tissues and cell lines was significantly compared with normal tissues and cell lines, respectively. The expression level of MEG3 was related to clinical stage, lymph node metastasis, distant metastasis and survival status. Overexpression of lncRNA MEG3 inhibited the proliferation, migration, and invasion of SCC25 and CAL27 cell lines, induced apoptosis and promoted the expression of p53 gene. lncRNA MEG3 played the role of a tumor inhibitor gene and significantly inhibited the biological activity of OSCC cell lines, which may provide a novel idea for molecular targeted therapy of OSCC.
RESUMEN
Oral squamous cell carcinoma (OSCC) is the leading cause of death in patients with head and neck cancer. Reliable biomarkers to guide treatment decisions for OSCC remain scarce. The purpose of this study was to identify novel prognostic markers regulated by super enhancers in OSCC. Eight modules were obtained by weighted gene co-expression network analysis (WGCNA), among which MEblue module had the highest correlation with tumor stage, alcohol consumption and smoking. There were 41 genes regulated by super enhancers in MEblue module. Functional analysis showed that 41 super enhancer-regulated genes were involved in cancer progression. A total of twenty transcription factors of the 41 genes were predicted. Prognostic analysis of the 41 genes and the top 5 transcription factors showed that patients with high expression of AHCY, KCMF1, MANBAL and TFDP1 had a poor prognosis. Immunohistochemical analysis showed that AHCY, KCMF1 and MANBAL were highly expressed in OSCC tissue. Cellular experiment demonstrated that TFDP1 promoted AHCY, KCMF1 and MANBAL expression by binding to the super enhancers of these genes. Knockdown of TFDP1, AHCY, KCMF1 and MANBAL inhibited the proliferation of OSCC cells. In conclusion, AHCY, KCMF1 and MANBAL were recognized as super enhancer-regulated prognostic biomarkers regulated by TFDP1 in OSCC.