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April 5, 2026Cancer Research1 citations

Abstract 1366: CYP4A22-AS1-YBX1 axis drives radiation resistance in cervical adenocarcinoma via PGK1 transactivation.

MZMingyi ZhouThe University of Texas MD Anderson Cancer Center CLChunlai LiThe University of Texas MD Anderson Cancer Center CICristina IvanThe University of Texas MD Anderson Cancer Center

Key Points

This research aims to uncover the molecular mechanisms of radiation resistance in cervical adenocarcinoma, particularly focusing on the CYP4A22-AS1 and YBX1 interaction.
Integrative analysis of TCGA and RNA-seq data to identify upregulated lncRNAs.
Confirmed CYP4A22-AS1 expression via qRT-PCR in tumor samples.
Utilized RNA pulldown and mass spectrometry to identify YBX1 as a binding partner.
Performed functional assays to assess the impact of silencing CYP4A22-AS1 and PGK1 on cell proliferation and radiosensitivity.
Validated findings using xenograft models.
CYP4A22-AS1 was significantly overexpressed in cervical adenocarcinoma compared to normal tissue.
High levels of CYP4A22-AS1 and PGK1 correlated with poorer disease-free survival.
CYP4A22-AS1 enhances YBX1’s nuclear locational translocation and promotes recruitment to the PGK1 promoter.
Knockdown of either CYP4A22-AS1 or PGK1 reduced cellular proliferation and increased radiosensitivity.

Abstract

Abstract Background: Cervical adenocarcinoma exhibits poor responsiveness to radiotherapy and inferior survival compared with squamous cell carcinoma. The molecular mechanisms underlying its intrinsic radiation resistance remain largely unknown. Methods: Integrative analysis of TCGA and our RNA-seq cohort identified CYP4A22-AS1 as one of the most upregulated lncRNAs in cervical adenocarcinoma. qRT-PCR confirmed higher CYP4A22-AS1 expression in tumors with short disease-free survival (DFS). RNA pulldown, mass spectrometry, and RIP assays defined YBX1 as a direct CYP4A22-AS1-binding partner. Immunofluorescence and ChIP-qPCR assays examined YBX1 nuclear localization and promoter occupancy of PGK1, respectively. Functional effects of CYP4A22-AS1, YBX1, and PGK1 silencing were assessed by CCK-8, colony, EdU, and TUNEL assays in HeLa and C33A cells, and validated in xenograft models. Results: CYP4A22-AS1 was markedly overexpressed in cervical adenocarcinoma relative to normal cervix. Clinically, high CYP4A22-AS1 and PGK1 levels correlated with shorter DFS. Mechanistically, CYP4A22-AS1 binds YBX1 and enhances its nuclear translocation, thereby promoting YBX1 recruitment to the PGK1 promoter and activating glycolytic metabolism. Knockdown of CYP4A22-AS1 or PGK1 suppressed proliferation and markedly increased radiosensitivity both in vitro and in vivo. Conclusions: This study identifies CYP4A22-AS1 as a novel oncogenic lncRNA that drives radiation resistance through YBX1-mediated PGK1 transactivation. Clinically, CYP4A22-AS1 overexpression predicts poor outcome, while its inhibition restores radiation sensitivity. Targeting the CYP4A22-AS1-YBX1-PGK1 signaling axis offers a promising therapeutic strategy to overcome radioresistance in cervical adenocarcinoma. Citation Format: Mingyi Zhou, Chunlai Li, Cristina Ivan, Simone Anfossi, Linda Fabris, Melanie Winkle, Recep Bayraktar, Meng Chen, Lan Pang, Masayoshi Shimizu, Francois Claret, George Calin, . CYP4A22-AS1-YBX1 axis drives radiation resistance in cervical adenocarcinoma via PGK1 transactivation abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1366.

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