West China Journal of Stomatology ›› 2021, Vol. 39 ›› Issue (3): 320-327.doi: 10.7518/hxkq.2021.03.012

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Effect of the regulator of G-protein signaling 2 on the proliferation and invasion of oral squamous cell carcinoma cells and its molecular mechanism

Lin Chengzhong1(), Liu Zheqi2, Zhou Wenkai2, Ji Tong2, Cao Wei2()   

  1. 1.The 2nd Dental Center, Ninth People, s Hospital, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Disease; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China
    2.Dept. of Oral and Maxillofacial-Head and Neck Oncology, Ninth People, s Hospital, Shanghai Jiao Tong University, School of Medicine; National Clinical Research Center for Oral Disease; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China
  • Received:2020-05-23 Revised:2021-02-15 Online:2021-06-01 Published:2021-05-26
  • Contact: Cao Wei E-mail:Evan-lin@sjtu.edu.cn;caowei561521@hotmail.com
  • Supported by:
    The National Natural Science Foundation of China(81672745)

Abstract: Objective

This study aims to investigate the effect of the regulator of G-protein signaling 2 (RGS2) on the proliferation and invasion of oral squamous cell carcinoma (OSCC) cells and its potential molecular mechanism. Metho?ds The expression status and clinical significance of RGS2 in head and neck squamous cell carcinomas and matched adjacent normal tissues were evaluated using TCGA database. Three OSCC cell lines (i.e., SCC-9, Cal27, and Fadu) were overexpressed with RGS2, and the effect of RGS2 on cell proliferation and invasion was determined using the Transwell, clone formation, and cell counting kit (CCK)-8 assays. Moreover, the yeast two-hybrid scree-ning and co-immunoprecipitation (Co-IP) assays were conducted to detect the correlation of RGS2, four and a half LIM domains protein 1 (FHL1), and damage DNA-binding protein 1 (DDB1).

Results

The expression level of RGS2 in OSCC was significantly lower than that in matched adjacent normal tissues (P=0.023). The high RGS2 expression level was negatively correlated with lymphovascular invasion (P<0.001). After transfection with lentiv-RGS2, the expression of RGS2 was increased, and the invasion and proliferation abilities of OSCC cell lines were evidently inhibited. FHL1 could competitively bind with RGS2, which decreased the integration of DDB1 and RGS2, inhibited the ubiquitination process of RGS2, and maintained the stability of the RGS2 protein.

Conclusion

RGS2 plays an important role in the inhibition of OSCC proliferation and invasion. The structure stability of RGS2 is competitively regulated by FHL1 and DDB1.

Key words: oral squamous cell carcinoma, regulator of G-protein signaling 2, proliferation, invasion, four and a half LIM domains protein 1, ubiquitination

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