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PSIP1 promotes gefitinib resistance in lung adenocarcinoma by inducing the expression of WASF3 and its downstream ITGB3/AKT signaling.
Wu, Shujun; Liu, Ying; Wang, Xi; Ren, Yanbei; Li, Xianghong; Wang, Huan.
Afiliação
  • Wu S; Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, China.
  • Liu Y; Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, China.
  • Wang X; Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, China.
  • Ren Y; Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, China.
  • Li X; Department of Respiratory Medicine, Xinmi First People's Hospital, Zhengzhou, China.
  • Wang H; Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, China. wanghuanyisheng@163.com.
Clin Transl Oncol ; 2024 Jul 30.
Article em En | MEDLINE | ID: mdl-39080187
ABSTRACT

BACKGROUND:

Gefitinib (GR), a representative drug of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is a key pillar in the treatment of lung adenocarcinoma (LUAD), but drug resistance is universal. Identifying the potential factors of drug resistance to GR is essential to treat patients with EGFR mutant LUAD.

METHODS:

The GR-resistant LUAD cells were established and confirmed by MTT assay. The effects of PC4 and SRSF1 interacting protein 1 (PSIP1) on GR-resistant cell proliferation and apoptosis in vitro and in vivo were detected by colony formation, flow cytometry, tumor-bearing animal model, immunohistochemistry, and TUNEL staining. Western blotting and qPCR were used to determine the expression of relevant markers. The effect of PSIP1 on the promoter region of Wiskott-Aldrich syndrome protein family member 3 (WASF3) was detected by the dual-luciferase assay. The interaction between PSIP1 and RNA polymerase II was evaluated using ChIP-qPCR and Co-IP assays.

RESULTS:

PSIP1 was highly enriched in GR-resistant LUAD cells. Downregulation of PSIP1 expression significantly inhibited the proliferation of LUAD-resistant cells and promoted apoptosis. WASF3 was shown to have similar effects as PSIP1 in promoting drug resistance in LUAD cells. PSIP1 promoted the transcriptional activity of WASF3, which was achieved by increasing RNA polymerase II recruitment on the WASF3 promoter. Furthermore, PSIP1 positively regulated the expression of the pro-EGFR-TKI resistance factor integrin subunit beta 3 (ITGB3).

CONCLUSION:

Our work suggests that PSIP1 promotes resistance to GR in LUAD cells by inducing the expression of WASF3 and its downstream regulator ITGB3.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Clin Transl Oncol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Itália
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Clin Transl Oncol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Itália