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. 2025 Dec;63(6):5641-5655.
doi: 10.1007/s10528-024-11011-0. Epub 2024 Dec 28.

LncRNA PGM5-AS1 Impairs the Resistance of Cervical Cancer to Cisplatin by Regulating the Hippo and PI3K-AKT Pathways

Huimin Wang #  1 , Yi Yang #  1 , Enjing Zhang  2 , Dan Wang  1 , Weiqiong Cai  3 , Chun Li  1 , Qiong Wei  4
Affiliations

LncRNA PGM5-AS1 Impairs the Resistance of Cervical Cancer to Cisplatin by Regulating the Hippo and PI3K-AKT Pathways

Huimin Wang et al. Biochem Genet. 2025 Dec.

Abstract

Cisplatin, a platinum-based chemotherapeutic agent, can be used to treat cervical cancer (CC), but cisplatin resistance is increased during the cisplatin treatment. Long non-coding RNA PGM5-AS1 reportedly participates in CC tumorigenesis; however, its role in CC patients with cisplatin resistance has not been revealed. The present aimed to examine the role of PGM5-AS1 in modulating cisplatin resistance in CC. The PGM5-AS1 expression in CC tissues from 29 patients was quantified using quantitative reverse transcription-polymerase chain reaction. The cisplatin-resistant CC cells were constructed by using increasing cisplatin concentrations. The effects of cisplatin resistance interacting with PGM5-AS1 on CC cell malignancy were confirmed by performing Cell Counting Kit 8, colony formation, wound healing, and transwell assays. The key proteins of the Hippo and PI3K-AKT signaling pathways were evaluated by Western blotting. PGM5-AS1 with low expression in CC tissues was correlated to higher International Federation of Gynecology and Obstetrics stage, poor differentiation, lymph node metastasis, and cisplatin resistance. PGM5-AS1 overexpression suppressed the proliferation, migration, and invasion abilities of cisplatin-resistant CC cells. Additionally, PGM5-AS1 overexpression in cisplatin-resistant CC cells could induce the activation of the Hippo signaling pathway and the inactivation of the PI3K-AKT signaling pathway. PGM5-AS1 enhanced the CC cell's sensitivity to cisplatin by activating the Hippo signaling pathway and inactivating the PI3K-AKT signaling pathway. Our study data may provide a novel therapeutic biomarker to overcome cisplatin resistance in CC treatment.

Keywords: Cervical cancer; Cisplatin; Hippo; PGM5-AS1; PI3K-AKT.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no conflicts of interest to disclose. Ethical Approval: The study received approval from the Ethics Committee of Wuhan Third Hospital (Tongren Hospital of Wuhan University). All clinical samples were handled in full compliance with the ethical standards outlined in the Declaration of Helsinki. Written informed consent was obtained from all patients involved in the study.

References

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