Study on the mechanism of miR-203a-3p targeting LPP to regulate the progression of tongue squamous cell carcinoma

Zhang Yalin

Cui Zifeng

Peng Shixiong

Wang Jinhang

Department of Stomatology, The Second Hospital of Shijiazhuang

Abstract:Objective To investigate the expression, biological function, and molecular mechanism of mi R-203a-3p in tongue squamous cell carcinoma(TSCC), with a focus on whether it suppresses TSCC progression by targeting LPP. Methods A total of 15 paired TSCC and adjacent normal tissues were collected for mi R-203a-3p expression analysis using q PCR.HSC3 cells were transfected with mi R-203a-3p mimics, and their proliferative, migratory, and invasive capabilities were evaluated. The interaction between mi R-203a-3p and LPP was validated via bioinformatics prediction, dual-luciferase reporter assay,q PCR, and Western blotting. LPP rescue experiments were performed to further explore its role in mi R-203a-3p-mediated phenotypic regulation. Results Compared with normal tissues, mi R-203a-3p expression was significantly reduced in TSCC tissues(t/P = 3.975/0.001). In HSC3 cells, overexpression of mi R-203a-3p significantly inhibited proliferation(t/P = 6.656/0.003),migration(t/P = 14.606/<0.001), and invasion(t/P = 11.056/<0.001) relative to the negative control(NC-mimics) group. Bioinformatic analyses and luciferase reporter assays showed that mi R-203a-3p directly targets the LPP 3'UTR(co-transfection of mi R-203a-3p mimics with LPP-WT vs. NC-mimics with LPP-WT, q/P = 23.052/<0.001), negatively regulating LPP m RNA(mi R-203a-3p mimics vs. NC-mimics, t/P = 15.589/<0.001) and protein expression. Overexpression of LPP partially rescued the mi R-203a-3p-mediated suppression of HSC3 cell proliferation(miR-203a-3p mimics + pc DNA3.1-LPP vs. mi R-203a-3p mimics + pc DNA3.1,q/P = 4.280/0.049), migration(q/P = 7.475/0.005), and invasion(q/P = 17.221/<0.001), indicating that LPP is an important functional downstream target of mi R-203a-3p. Conclusion mi R-203a-3p suppresses TSCC cell proliferation,migration, and invasion by directly targeting and downregulating LPP. The mi R-203a-3p/LPP axis plays a crucial regulatory role in TSCC progression and may serve as a potential target for early diagnosis and therapeutic intervention.

Keyword:Tongue squamous cell carcinomami R-203a-3pLPPMechanismTargeted therapy

Fund:Medical Science Research Project of Hebei (20240889)