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

Yuhua Huang; Wei Wu; Xing Zhang

doi:10.1016/j.archoralbio.2024.105979

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

Arch Oral Biol. 2024 Apr 22:164:105979. doi: 10.1016/j.archoralbio.2024.105979. Online ahead of print.

Authors

Yuhua Huang¹, Wei Wu¹, Xing Zhang²

Affiliations

¹ Department of Stomatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 6/F, East Zone, No. 111, Dade Road, Yuexiu District, Guangzhou, Guangdong 510120, China.
² Department of Stomatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 6/F, East Zone, No. 111, Dade Road, Yuexiu District, Guangzhou, Guangdong 510120, China. Electronic address: drzhangxing@hotmail.com.

PMID: 38744201
DOI: 10.1016/j.archoralbio.2024.105979

Abstract

Objective: The study aimed to investigate the effects of verbascoside on oral squamous cell carcinoma (OSCC) cellular behaviors and underlying molecular mechanisms.

Design: 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.

Results: 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.

Conclusions: 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.

Keywords: Invasion; METTL3; MiR-31–5p/HIPK2; Migration; Oral squamous cell carcinoma; Verbascoside.