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

doi:10.7518/hxkq.2021.03.012

Abstract

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

CLC Number:

R 782

Lin Chengzhong, Liu Zheqi, Zhou Wenkai, Ji Tong, Cao Wei. Effect of the regulator of G-protein signaling 2 on the proliferation and invasion of oral squamous cell carcinoma cells and its molecular mechanism[J]. West China Journal of Stomatology, 2021, 39(3): 320-327.

Figures/Tables 6

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Tab 1

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References 19

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分组	例数（%）（n=514）	RGS2 表达		P值
分组	例数（%）（n=514）	低表达（%）（n=257）	高表达（%）（n=257）	P值
性别				0.109
女性	135（26.3）	59（11.5）	76（14.8）
男性	379（73.7）	198（38. 5）	181（35.2）
解剖部位
口腔	309（60.1）	148（28.8）	161（31.3）	0.684
口咽	80（15.6）	44（8.55）	36（7.05）
喉	115（22.4）	60（11.7）	55（10.7）
下咽	10（1.9）	5（0.95）	5（0.95）
淋巴血管侵犯
有	121（23.5）	55（10.7）	66（12.8）	<0.001
无	223（43.4）	92（17.9）	131（25.5）
不明确	170（33.1）	110（21.4）	60（11.7）
神经侵犯
有	168（32.7）	81（15.8）	87（16.9）	0.098
无	190（37.0）	87（16.9）	103（20）
不明确	156（30.4）	89（17.3）	67（13.1）
组织学分级
高分化	61（11.8）	30（5.8）	31（6.0）	0.563
中/低分化	431（83.8）	213（41.4）	218（42.4）
不明确	22（4.4）	14（2.8）	8（1.6）
原发肿瘤（T）
最大径≤4 cm（T1~T2）	188（36.6）	98（19.1)	90（17.5）	0.607
最大径>4 cm（T3~T4）	316（61.5）	153（29.8）	163（31.7）
不明确	10（1.9）	6（1.1）	4（0.8）
颈淋巴结转移（N）
无	251（48.8）	122（23.7）	129（25.1）	0.746
有	251（48.8）	128（24.9）	123（23.9）
不明确	12（2.4）	7（1.4）	5（1.0）
临床分期（TNM）
Ⅰ-Ⅱ	117（22.8）	67（13.0）	50（9.7）	0.203
Ⅲ-Ⅳ	383（74.5）	183（35.6）	200（38.9）
不明确	14（2.7）	7（1.4）	7（1.4）

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