Int J Stomatol

Int J Stomatol ›› 2026, Vol. 53 ›› Issue (4): 526-536.doi: 10.7518/gjkq.2026228

• Original Article • Previous Articles    

Regulation of the progression of oral squamous cell carcinoma by 5-hydroxytryptamine receptor 2C via the Gαq/11-Yes-associated protein signaling pathway

Zhenyu Zhang(),Mei Huang,Hao Cui,Silu Sun,Xiaobo Luo,Lu Jiang,Yuchen Jiang()   

  1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management & Dept. of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2025-02-18 Revised:2025-12-23 Online:2026-07-01 Published:2026-06-25
  • Contact: Yuchen Jiang E-mail:zhenyuzhang7@outlook.com;jiangyuchen16@126.com
  • Supported by:
    National Natural Science Foundation of China(82002888)

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Abstract:

Objective　To investigate the regulatory effect of 5-hydroxytryptamine receptor 2C (HTR2C) on oral squamous cell carcinoma (OSCC) through the Gαq/11-Yes-associated protein (YAP) signaling pathway.Me-thods　The TCGA database was used to analyze the expression of HTR2C in OSCC and normal oral tissues and its relationship with the overall survival rate of patients. The expression level of HTR2C was detected in OSCC tumor microarrays through immunohistochemistry, and the correlation between HTR2C and clinicopathological features was analyzed. HTR2C knockdown HN12 and UM1 cell lines were constructed, and the effects of HTR2C knockdown or its inhi-bitor (Puerarin) on the proliferation, migration, and invasion of OSCC cells were evaluated through cell counting kit-8, colony formation, wound healing, and Transwell assays. Western blot analysis, quantitative real-time polymerase chain reaction, and immunofluorescence were used to detect the expression and activation of the HTR2C-Gαq/11-YAP signaling pathway. The effect of HTR2C on the growth of OSCC was verified by using a subcutaneous xenograft model of OSCC in nude mice. Results　HTR2C was significantly overexpressed in OSCC tissues, and its high expression was significantly associated with the poor prognosis of patients (P<0.05). In vitro experiments demonstrated that the knockdown of HTR2C or use of Puerarin significantly inhibited the proliferation and clonal formation, migration, and invasion abilities of OSCC cells (P<0.01), and the inhibitory effect of puerarin was dose-dependent. Mechanism studies showed that HTR2C knockdown inhibited YAP phosphorylation at Tyr357 and promoted YAP phosphorylation at Ser127 by reducing the phosphorylation of focal adhesion kinase and Cofilin, thereby inhibiting YAP transcriptional activity and decreasing the expression of its downstream target genes CYR61, CTGF, and AURKA (P<0.05). In vivo experiments confirmed that inhibiting the expression of HTR2C by using Puerarin could significantly inhibit the growth of OSCC xenograft tumors (P<0.000 1). This effect was achieved by regulating the YAP signaling pathway. Conclusion　The high expression of HTR2C in OSCC was significantly associated with poor prognosis. HTR2C may regulate the proliferation, migration, invasion, and tumorigenesis of OSCC cells by activating the Gαq/11-YAP signaling pathway. This study suggests that HTR2C may be a potential therapeutic target for OSCC. However, further clinical research is needed to validate its findings.

Key words: oral squamous cell carcinoma, 5-hydroxytryptamine receptor 2C, Gαq/11-Yes-associated protein signaling pathway, Yes-associated protein, Puerarin, tumor progression

CLC Number: 

  • R739.8

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Fig 1

Representative IHC staining of HTR2C and YAP in OSCC and control tissues"

Fig 2

Expression of HTR2C in OSCC and its correlation with prognosis"

Fig 3

Knocking down HTR2C in vitro can significantly inhibit the proliferation, migration and invasion of OSCC cells"

Fig 4

HTR2C promotes the malignant progression of OSCC cells by activating Gαq/11-YAP signaling pathway"

Fig 5

HTR2C inhibitor significantly inhibited the proliferation, migration and invasion of OSCC cells"

Fig 6

HTR2C inhibitor effectively inhibited the growth of subcutaneous xenograft tumors in vivo"

Fig 7

Schematic diagram of HTR2C in the regulation of the Gαq/11-YAP signaling pathway in OSCC"

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