Home General Physiology and Biophysics 2024 General Physiology and Biophysics Vol.43, No.3, p 243–253, 2024

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Founded: 1982
ISSN 1338-4325 (online)
ISSN 0231-5882 (print)
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General Physiology and Biophysics Vol.43, No.3, p 243–253, 2024

Title: KRAS depletion suppresses ferroptosis and affects Hippo pathway in cataract
Author: Hongda Jiang, Yinggui Yu, Yu Yan

Abstract: Cataract, a painless and progressive disorder is manifested as the opacification of the lens that represents the most significant cause of blindness worldwide. The objective of this study is to unveil the function of Kirsten rat sarcoma (KRAS) and potential action mechanisms against cataract. The ferroptosis-associated differentially expressed genes (DEGs) and pivot genes were extracted through the comprehensive bioinformatics methods. Erastin was applied for inducing ferroptosis in hydrogen peroxide (H2O2)-treated SRA01/04 cells, and validated by detecting content of intracellular iron, glutathione (GSH), malondialdehyde (MDA). Additionally, the effects of KRAS deficiency on ferroptosis were determined by functional assays. The proteins expression related to ferroptosis and Hippo pathway were determined by Western blotting. A total of 73 ferroptosis-related DEGs were discovered, and 6 critical core genes were confirmed upregulation in cataract cell model. The H2O2-treated SRA01/04 cells exhibited decrease of cell viability and proliferation, iron accumulation, MDA increase, GSH consumption, rise of COX2 and decline of GPX4, with further aggravated under erastin treatment, while the phenomena were improved by KRAS knockdown. Additionally, KRAS deficiency was involved in the Hippo signalling pathway activation. Downregulation of KRAS might restrain ferroptosis and affect Hippo pathway in cataract.

Keywords: Cataract — KRAS — Ferroptosis — Hippo pathway — Bioinformatics
Published online: 16-May-2024
Year: 2024, Volume: 43, Issue: 3 Page From: 243, Page To: 253
doi:10.4149/gpb_2024009


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