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  • Title: PARP-1 induces EMT in non-small cell lung carcinoma cells via modulating the transcription factors Smad4, p65 and ZEB1.
    Author: Kumar M, Jaiswal RK, Prasad R, Yadav SS, Kumar A, Yadava PK, Singh RP.
    Journal: Life Sci; 2021 Mar 15; 269():118994. PubMed ID: 33417952.
    Abstract:
    AIM: To study the role of PARP-1 in EMT of non-small cell lung carcinoma. MATERIALS AND METHODS: We used H1299 and H460 lung cancer cells for knockdown study of PARP-1 using shPARP-1 lentiviral particle. We performed western blotting, confocal microscopy, semi-quantitative PCR, wound healing and colony formation assays. BACKGROUND AND KEY FINDINGS: PARP-1 (poly-ADP ribose polymerase-1) is a multi-domain protein having DNA binding, auto-modification and catalytic domain, that participates in many biological processes including DNA damage detection and repair, transcription regulation, apoptosis, necrosis, cancer progression and metastasis. Metastasis is a leading cause of death in cancer patients, which starts in epithelial tumors via initiating epithelial to mesenchymal transition. There are various transcription factors involved in EMT including Snail-1, Smads, p65, ZEB1 and Twist1. We studied the effect of PARP-1 knockdown on EMT in non-small cell lung cancer cell line H1299. We found a significant increase in epithelial marker including ZO1 and β-catenin, while prominent decrease in the mesenchymal marker vimentin after PARP-1 knockdown in H1299 cells. Transcription factors including p65, Smad4 and ZEB1 showed significant decrease with concurrent expression of EMT markers. Cell migration and colony formation decreased after PARP-1 knockdown in H1299 cells. SIGNIFICANCE: Overall, the shRNA mediated knockdown of PARP-1 in H1299 cells resulted in reversal of EMT or mesenchymal to epithelial transition (MET) characterized by an increase in epithelial markers and a decrease in mesenchymal markers, via down-regulating transcription factors including Smad4, p65 and ZEB1. Thus PARP-1 has a role in EMT in lung cancer.
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