METTL3-Mediated Maturation of miR-99a-5p Promotes Cell Migration and Invasion in Oral Squamous Cell Carcinoma by Targeting ZBTB7A.

METTL3 is an important methyltransferase in N(6)-methyladenosine (m6A) modification. Recently, METTL3 mediates methylation of pri-microRNA (miRNA) to accelerate miRNA maturation, regulating tumor development. This study explored whether METTL3 mediated miR-99a-5p to influence oral squamous cell carcinoma (OSCC) cell metastasis. MiR-99a-5p, ZBTB7A, and MATTL3 expression was measured using quantitative real-time PCR. Biological behaviors were assessed using cell counting kit-8, flow cytometry, Transwell assay, as well as western blot. Luciferase reporter assay evaluated the interaction between miR-99a-5p and ZBTB7A. METTL3-regulated pri-miR-99a-5p processing was determined by RNA binding protein immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP) assays. The consequences clarified that miR-99a-5p was upregulated in OSCC cells. Downregulation of miR-99a-5p suppressed cellular viability, migration, invasion, and epithelial-mesenchymal transition (EMT), and induced apoptosis. ZBTB7A acted as a miR-99a-5p target and reversed the effects on cellular behaviors induced by miR-99a-5p inhibitor. m6A content and METTL3 expression were increased in OSCC cells. METTL3 promoted the m6A modification of pri-miR-99a-5p and thereby facilitated miR-99a-5p processing. Moreover, knockdown of METTL3 inhibited OSCC metastasis by downregulating miR-99a-5p. Taken together, METTL3 promoted miR-99a-5p maturation in an m6A-dependent manner, which further targets ZBTB7A to accelerate the progression of OSCC. These findings suggest potential targets for OSCC therapy.

Huang Y ，Guan Y ，Zhang X 《-》

Verbascoside inhibits oral squamous cell carcinoma cell proliferation, migration, and invasion by the methyltransferase 3-mediated microRNA-31-5p/homeodomain interacting protein kinase 2 axis.

The study aimed to investigate the effects of verbascoside on oral squamous cell carcinoma (OSCC) cellular behaviors and underlying molecular mechanisms. For this purpose, SCC9 and UM1 cell lines were treated with verbascoside, and their biological behaviors, including proliferation, migration, and invasion, were evaluated using cell counting kit-8, 5-Ethynyl-2'-deoxyuridine, and Transwell assays. The expression of methyltransferase-3 (METTL3), microRNA (miR)- 31-5p, and homeodomain interacting protein kinase-2 (HIPK2) were examined using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between METTL3 and miR-31-5p was evaluated by RNA immunoprecipitation and methylated RNA immunoprecipitation, while the interaction between miR-31-5p and HIPK2 was evaluated by dual-luciferase reporter analysis. The results indicated inhibition of OSCC cell proliferation, migration, and invasion post verbascoside treatment. Similarly, METTL3 was upregulated in OSCC cells and was inhibited post-verbascoside treatment. Overexpressing METTL3 promoted the cellular processes. Moreover, miR-31-5p was upregulated in OSCC cells, where METTL3 facilitated the processing of miR-31-5p in an N6-methyladenosine (m6A)-dependent manner. The HIPK2 served as miR-31-5p target, where overexpressing miR-31-5p or HIPK2 knockdown reversed the suppression of verbascoside-induced biological behaviors. Verbascoside inhibited the progression of OSCC by inhibiting the METTL3-regulated miR-31-5p/HIPK2 axis. These findings suggested that verbascoside might be an effective drug for OSCC therapy.

Huang Y ，Wu W ，Zhang X 《-》

Mechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer.

Liang X ，Zhang Z ，Wang L ，Zhang S ，Ren L ，Li S ，Xu J ，Lv S ... -  《-》

hsa_circ_0072387 Suppresses Proliferation, Metastasis, and Glycolysis of Oral Squamous Cell Carcinoma Cells by Downregulating miR-503-5p.

Han L ，Cheng J ，Li A 《-》

MicroRNA-99a-5p suppresses cell proliferation, migration, and invasion by targeting isoprenylcysteine carboxylmethyltransferase in oral squamous cell carcinoma.

Sun X ，Yan H 《-》