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MedComm

IF: 10.69
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Inhibition of Selenoprotein I promotes ferroptosis and reverses resistance to platinum chemotherapy by impairing Akt phosphorylation in ovarian cancer

Published:11 December 2024 DOI: 10.1002/mco2.70033 PMID: 39669976
Jing Li,?Mimi Chen,?Dingwen Huang,?Ziyin Li,?Yu Chen,?Jinhua Huang,?Yuanqun Chen,?Zhili Zhou,?Zhiying Yu

Abstract

Ovarian cancer (OV) ranks among the deadliest gynecological cancer, known for its high risk of relapse and metastasis, and a general resistance to conventional platinum-based chemotherapy. Selenoprotein I (SELENOI) is a crucial mediator implicated in human hereditary spastic paraplegia. However, its role in human tumors remains poorly elucidated. Here, we comprehensively analyzed SELENOI expression patterns, functions, and clinical implications across various malignancies through the integration of bulk transcriptomics, cancer databases, and in vitro and in vivo experiments. Pan-cancer analysis indicated upregulated SELENOI expression across various cancers, correlating with augmented malignancy, suppressed tumor immunity and poor prognosis. Knockdown of SELENOI caused G0/G1-phase cell cycle arrest and diminished aggressive cancer phenotypes in OV cells. Moreover, SELENOI inhibition augments ferroptosis and reverses the cisplatin resistance in OV cells by modulating Akt phosphorylation. Conversely, overexpression of SELENOI in OV cells enhanced therapeutic sensitivity to cisplatin by upregulating Akt phosphorylation. Importantly, in vivo studies demonstrated that SELENOI inhibition suppressed ovarian tumor growth and enhanced cisplatin's anticancer effects. These findings highlight the significant role of SELENOI in OV by modulating ferroptosis and chemotherapy resistance. Targeting SELENOI represents a promising therapeutic approach to promote the efficacy of platinum-based chemotherapy in OV, particularly in cases of resistance.

Substances (7)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Cisplatin 15663-27-1 Cl2H6N2Pt 770 suppliers $17.00-$6890.00
Rosiglitazone 122320-73-4 C18H19N3O3S 474 suppliers $12.00-$970.00
Celastrol 34157-83-0 C29H38O4 410 suppliers $39.00-$1390.00
Propidium iodide 25535-16-4 C27H34IN4+ 295 suppliers $29.00-$1780.00
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 153 suppliers $44.00-$2691.10
GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE 9001-50-7 C3H7O6P 127 suppliers $69.60-$921.00
PUROMYCIN 53-79-2 C22H29N7O5 91 suppliers $73.60-$1200.00

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