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. 2025 Jun 17;56(4):196.
doi: 10.1007/s10735-025-10473-9.

EIF4A3-Mediated downregulation of circPTEN promotes hepatocellular carcinoma progression through the miR-1289/RBM38 Axis

Shuo Yu  1 , Min Wang  1 , Feng Peng  1 , Hang Zhang  1 , Renyi Qin  2 , Chengjian Shi  3
Affiliations

EIF4A3-Mediated downregulation of circPTEN promotes hepatocellular carcinoma progression through the miR-1289/RBM38 Axis

Shuo Yu et al. J Mol Histol. .

Abstract

Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide. Our research endeavored to delineate the role of circPTEN and to assess its potential as a prognostic biomarker in HCC. CircPTEN expression was quantified in HCC cells and clinical specimens using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The effects of circPTEN overexpression on cellular activities were evaluated through Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EDU), and Transwell assays. The impact of circPTEN overexpression on HCC tumorigenesis and metastasis was also assessed in xenograft mouse models. Kaplan-Meier survival analysis was conducted to assess circPTEN's prognostic value, while additional experiments were conducted to examine the circPTEN-microRNA-1289 (miR-1289) interaction and Eukaryotic Initiation Factor 4A3 (EIF4A3) regulatory effect on circPTEN expression. Our investigations revealed significantly reduced circPTEN expression in HCC, with lower levels correlating with poorer patient outcomes. In vitro experiments demonstrated that enhancing circPTEN expression could inhibit both the proliferation and invasiveness of HCC cells. At the molecular level, circPTEN functioned as a microRNA sponge for miR-1289, consequently upregulating RNA Binding Motif Protein 38 (RBM38), a validated tumor suppressor in HCC. Furthermore, EIF4A3 was identified as a negative regulator of circPTEN expression in HCC cells. Nude mouse model experiments corroborated our in vitro results, showing that increased circPTEN expression corresponded with reduced tumorigenesis and metastatic spread. CircPTEN functions as a tumor suppressor in HCC, regulating the miR-1289/RBM38 axis while being negatively regulated by EIF4A3. Restoration of circPTEN expression represents a potential therapeutic strategy for HCC, and circPTEN levels may serve as a candidate prognostic biomarker.

Keywords: Circular RNA; EIF4A3; Hepatocellular Carcinoma; RBM38; Tumor suppressor gene; miR-1289.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval and consent for participation: The study was approved by the Ethics Committee of Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, all methods were performed in accordance with the Declarations of Helsinki. Written informed consents were signed by all participants before the study. Each experiment was performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals. The study was carried out in compliance with the ARRIVE guidelines ( https://arriveguidelines.org ). Consent for publication: Not applicable.

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