2. Academic Validation
  3. Shp2 regulates the trophoblast cell cycle progression through p53-p21 pathway modulation

Shp2 regulates the trophoblast cell cycle progression through p53-p21 pathway modulation

  • Biochem Biophys Res Commun. 2025 Aug 30:776:152209. doi: 10.1016/j.bbrc.2025.152209.
Ming-Hui Meng 1,  Xin Wu 1,  Ting Qin 1,  Wei-Ying Mo 1,  Xi-Gui Long 1,  Ying Li 1,  Peng Zhang 1,  Jian-Ning Lu 2,  Dongjin Pan 3,  Xiu-Qun Zhang 4
Affiliations

Affiliations

  • 1 Medical Genetics and Prenatal Diagnosis Center, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China.
  • 2 Obstetrics Department, Fusui County People's Hospital, Chongzuo, 512199, China.
  • 3 College of Food and Quality Engineering, Nanning University, Nanning, 530200, China. Electronic address: pandongjin@unn.edu.cn.
  • 4 Medical Genetics and Prenatal Diagnosis Center, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China. Electronic address: suerise@163.com.
PMID: 40527180 DOI: 10.1016/j.bbrc.2025.152209
Abstract

Normal trophoblast cells proliferation and migration are crucial for placental development. Dysfunction in these processes is closely linked to pregnancy-related diseases, such as preeclampsia (PE) and fetal growth restriction (FGR). This study aimed to explore the role of Src homology 2 domain-containing protein tyrosine Phosphatase 2 (SHP2) in regulating trophoblast cell HTR-8/SVneo (HTR8) functions and its underlying mechanisms. By using a specific SHP2 Inhibitor (SHP099) and lentivirus-mediated SHP2 knockdown combined with transcriptome Sequencing, we found that SHP2 inactivation significantly inhibited HTR8 proliferation by inducing G0/G1 cell cycle arrest and reduced migratory/invasive capacities. The transcriptomic study revealed that SHP2 knockdown in HTR8 cells significantly upregulated p53 pathway downstream genes (CDKN1A, MDM2, etc.). Western blot results showed that SHP2 downregulation increased p21 protein levels, suggesting that SHP2 probably maintains cell cycle progression by suppressing the p53-p21 axis. Both pharmacological inhibition and genetic knockdown of SHP2 modulated ERK1/2 and Akt activities, indicating its roles in trophoblast functions through MAPK and PI3K-Akt signaling. This study provides new insights into the molecular mechanisms governing trophoblast biology and potential therapeutic targets for placental disorders.

Keywords

Cell cycle; Placenta; Shp2; Trophoblast; p53 pathway.

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