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A novel HPV E6/E7-regulated long noncoding RNA CRL suppresses cervical intraepithelial neoplasia progression by attenuating ferroptosis.

Created on 22 Jun 2026

Authors

Ting Zhang, Yanan Yan, Shuai Yuan, Tianqi Yang, Can Shi

Published in

Human cell. Volume 39. Issue 7. Jun 21, 2026. Epub Jun 21, 2026.

Abstract

Sustained human papillomavirus (HPV) infection induces cervical intraepithelial neoplasia (CIN), a well-established precursor lesion and risk factor for cervical cancer. However, the specific long noncoding RNAs (lncRNAs) that regulate CIN progression remain poorly characterized. Herein, we identified a novel lncRNA, designated CIN-related lncRNA (CRL), and explored its role in CIN pathogenesis. Clinically, reduced CRL expression was significantly associated with advanced CIN stages, suggesting a potential correlation with disease severity. HPV oncoproteins E6 and E7 suppressed CRL expression through KDM2B-mediated modification of histone H3 lysine 4 trimethylation (H3K4me3). CRL repressed CIN progression and cell death in vitro. Further mechanistic investigations revealed that CRL exerted this inhibitory effect by suppressing ferroptosis. Importantly, CRL accelerated the degradation of transferrin receptor (TFRC) mRNA by interacting with the iron-sensing protein iron-responsive element-binding protein 2 (IREB2). Collectively, our findings highlight the functional importance of lncRNA CRL in HPV-induced CIN progression, specifically through its regulation of ferroptosis via the IREB2-TFRC axis. This study provides new insights into the molecular mechanisms underlying CIN development and identifies CRL as a potential candidate for CIN diagnosis or intervention.

PMID:
42323795
Bibliographic data and abstract were imported from PubMed on 22 Jun 2026.

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