Circular RNAs (circRNAs) have emerged as important regulators of carcinogenesis. However, the role of circRNAs in oral squamous cell carcinoma (OSCC) remains limited. Here, total RNAs were extracted from three pairs of OSCC and adjacent normal tissues and subjected to circRNA microarrays to detect the differentially expressed circRNAs. Gene Ontology (GO) and functional category analyses were used to identify circRNAs associated with tumor cell proliferation pathways. Then, gain-of-function assays or loss-of-function assays were conducted to investigate the functions of the most upregulated and downregulated circRNAs on TSCC1 cell proliferation, cell cycle and apoptosis using CCK-8 and EdU assays, flow cytometry and Hoechst 33258 staining, respectively. The results revealed that hsa_circRNA_102459 was significantly downregulated and hsa_circRNA_043621 was significantly upregulated in OSCC tissues. Clinical stage, tumor differentiation, lymph node metastasis presented significant difference in regards to the expression of circRNA_043621 and circRNA_102459. The in vitro experiments further demonstrated that upregulation of circRNA_102459 or downregulation of circRNA_043621 significantly suppressed TSCC1 cell proliferation, induced cell cycle G0/G1 phase arrest and promoted apoptosis. Furthermore, the MAPK and PI3K/Akt pathways were suppressed, while Bcl-2 family members were activated by circRNA_102459 overexpression and circRNA_043621 knockdown. Taken together, our study indicates that differentially expressed circRNAs are closely related to the carcinogenesis of OSCC. Among these, circRNA_102459 and circRNA_043621 may function as a tumor-suppressor and promoter, respectively, of OSCC carcinogenesis, and thus may be valuable diagnostic biomarkers of OSCC.

To explore the effects of lncRNA GACAT1/miR-149 molecular axis on the proliferation, apoptosis, migration and autophagy of oral squamous cell carcinoma (OSCC) cells, and to explore its molecular mechanism. The expressions of lncRNA GACAT1 and miR-149 in tissues and cell lines of patients with OSCC were detected by qRT-PCR. Si-control, GACAT1-siRNA, inhibitor NC and miR-149 inhibitors were transfected into OSCC cells separately or in combination with Lipofectamine 2000. The binding sites between lncRNA GACAT1 and miR-149 were predicted using the miRanda website, and the targeting relationship was verified by dual-luciferase assay. The expression of lncRNA XIST and miR-149 was detected by qRT-PCR. CCK-8 assay was used to detect cell activity. Cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration ability was detected by Transwell assay. The expression of migration and autophagy-related proteins was detected by western blot. LncRNA GACAT1 was highly expressed in cancer tissues and cell lines of OSCC patients ( P < 0.01), while miR-149 was low expressed ( P < 0.01). LncRNA GACAT1 binds to miR-149 targeting. The down-regulation of lncRNA GACAT1 inhibited the proliferation and migration of OSCC cells and promoted apoptosis and autophagy ( P < 0.01). The transfection of miR-149 inhibitor had the opposite effect. Knockdown of lncRNA GACAT1 and transfection with miR-149 inhibitor reversed the effect of GACAT1 silencing on OSCC cells. Inhibition of lncRNA GACAT1 can inhibit the proliferation and migration of OSCC cells, promote apoptosis and autophagy, and the mechanism may be related to the targeting of miR-149.

This study aimed to explore the role and mechanism of circ_0014359 in the OSCC. We firstly investigated the expression levels of circ_0014359 in OSCC tissues and cell lines. Then, the effects of knocking down circ_0014359 on cellular viability, apoptosis, migration, and invasion of OSCC cell lines were observed by cell counting kit-8 assay, flow cytometry, and transwell assay. Xenografts mouse model was established to explore the in vivo effect of circ_0014359 on the tumor volume and size of OSCC. We found that circ_0014359 was highly expressed in the OSCC tissues and cell lines compared to the normal controls (P<0.05). The expression of circ_0014359 was associated with the survival of patients (P<0.05). For the OSCC cell lines, circ_0014359 knock down induced apoptosis and inhibited migration, invasion, and epithelial-mesenchymal transition of OSCC cells (P<0.001). In vivo, silencing the circ_0014359 blocked the growth of OSCC tumors. The circ_0014359 can directly interact with the micro-RNA-149 (miR-149). Inhibition of miR-149 can rescue the inhibitory effects of circ_0014359 knock down on OSCC cells. The circ_0014359-miR-149 pathway may be a novel target for developing strategies for the diagnosis and treatment of OSCC.