ESM1 suppresses LncRNA GAS5/miR-23a-3p/PTEN axis to promote the cisplatin-chemotherapy resistance of ovarian cancer cells via activating the PI3K/AKT pathway.

Mar 17, 2025

Experts: Hui Li,Tingyu Fan,Mei Qin,Shuanghua Chen,Wenchao Zhou,Peiting Wu,Yuwei Yuan,Xing Tang,Tian Zeng,Jiawen Fang,Ting Yi,Juan Zhang,Juan Zou,Yukun Li

Cisplatin chemotherapy is an important treatment for advanced ovarian cancer (OC). However, the development of cisplatin resistance greatly limits the survival time of OC patients. Endothelial cell-specific molecule 1 (ESM1) has been found to be an important proto-oncogene promoting OC, but its mediating OC cisplatin resistance remains unknown.
We used quantitative polymerase chain reaction (qPCR) to measure transcription levels of ESM1, Growth arrest specific transcript 5 (GAS5), miR-23a-3p, and Phosphatase And Tensin Homolog (PTEN). A double luciferase reporter gene assay confirmed the direct binding of GAS5 to miR-23a-3p and miR-23a-3p to PTEN mRNA. The effects of ESM1, GAS5, miR-23a-3p, and PTEN on OC cisplatin resistance were tested with an Half Maximal Inhibitory Concentration (IC50) assay. Flow cytometry was used to assess the effects of ESM1, GAS5, and miR-23a-3p on cisplatin-induced OC apoptosis. Changes in apoptosis-related proteins and PI3K/AKT-related proteins were analyzed with western blot (WB).
ESM1 inhibits the levels of GAS5 and PTEN but increases miR-23a-3p. ESM1 and miR-23a-3p promote OC cisplatin resistance. GAS5 and miR-23a-3p promote cisplatin sensitivity for OC cells. Moreover, the main molecular mechanism is the ESM1/GAS5/miR-23a-3p/PTEN/PI3K/Akt signaling axis.
ESM1 promotes OC cisplatin resistance by activating the Phosphoinositide-3-Kinase (PI3K)/AKT Serine/Threonine Kinase (Akt) signaling pathway through the GAS5/miR-23a-3p/PTEN signaling axis. This suggests that prescriptive ESM1 regulates key downstream molecular mechanisms via non-coding RNA and can be used before neoadjuvant chemotherapy in OC is initiated.

© 2025. The Author(s).

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ABOUT THE EXPERTS

Hui Li,Tingyu Fan,Mei Qin,Shuanghua Chen,Wenchao Zhou,Peiting Wu,Yuwei Yuan,Xing Tang,Tian Zeng,Jiawen Fang,Ting Yi,Juan Zhang,Juan Zou,Yukun Li

Hui Li

Department of Assisted Reproductive Centre, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.

Tingyu Fan

Department of Assisted Reproductive Centre, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.

Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Hengyang Medical School, Cancer Research Institute, University of South China, Hengyang, Hunan, China.

Mei Qin

Department of Gynecology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.

Shuanghua Chen

Hunan Traditional Chinese Medicine College, Zhuzhou, Hunan, China.

Department of Infectious Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.

Wenchao Zhou

Department of Assisted Reproductive Centre, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.

Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Hengyang Medical School, Cancer Research Institute, University of South China, Hengyang, Hunan, China.

Peiting Wu

Department of Assisted Reproductive Centre, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.

Yuwei Yuan

Department of Assisted Reproductive Centre, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.

Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Hengyang Medical School, Cancer Research Institute, University of South China, Hengyang, Hunan, China.

Xing Tang

Department of Assisted Reproductive Centre, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.

Tian Zeng

Department of Assisted Reproductive Centre, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.

Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Hengyang Medical School, Cancer Research Institute, University of South China, Hengyang, Hunan, China.

Jiawen Fang

Nursing Class of 2022, School of Nursing, Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, China.

Ting Yi

Trauma Center, The Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, Hunan, China.

Juan Zhang

Department of Assisted Reproductive Centre, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China. zhangjuan@csu.edu.cn.

Juan Zou

Department of Assisted Reproductive Centre, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China. zoujuanusc@usc.edu.cn.

Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Hengyang Medical School, Cancer Research Institute, University of South China, Hengyang, Hunan, China. zoujuanusc@usc.edu.cn.

Yukun Li

Department of Assisted Reproductive Centre, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China. yukun_li@foxmail.com.