Evidence map›Paper›PMID 41488833›Full record

ArticleAnnals of gastroenterological surgery2026

Mechanism of Lenvatinib Resistance via Exosomal miRNA-132/Nrf2 Axis in Hepatocellular Carcinoma.

Chie Takasu, Chiharu Nakasu, Yu Saito, Yuji Morine, Tetsuya Ikemoto, Shinichiro Yamada, Hiroki Teraoku, Mitsuo Shimada

Abstract read
In one paragraph

Article in Annals of gastroenterological surgery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Chie TakasuDepartment of Surgery, Institute of Health Biosciences Tokushima University Tokushima Japan.ORCID https://orcid.org/0000-0001-6438-2763
Chiharu NakasuDepartment of Surgery, Institute of Health Biosciences Tokushima University Tokushima Japan.
Yu SaitoDepartment of Surgery, Institute of Health Biosciences Tokushima University Tokushima Japan.ORCID https://orcid.org/0000-0001-6349-1669
Yuji MorineDepartment of Surgery, Institute of Health Biosciences Tokushima University Tokushima Japan.ORCID https://orcid.org/0000-0002-5889-9288
Tetsuya IkemotoDepartment of Surgery, Institute of Health Biosciences Tokushima University Tokushima Japan.ORCID https://orcid.org/0000-0001-9800-1359
Shinichiro YamadaDepartment of Surgery, Institute of Health Biosciences Tokushima University Tokushima Japan.ORCID https://orcid.org/0000-0003-3847-751X
Hiroki TeraokuDepartment of Surgery, Institute of Health Biosciences Tokushima University Tokushima Japan.ORCID https://orcid.org/0000-0001-5730-9808
Mitsuo ShimadaDepartment of Surgery, Institute of Health Biosciences Tokushima University Tokushima Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Lenvatinib is a multiple receptor tyrosine kinase inhibitor and a first-line targeted therapy for hepatocellular carcinoma (HCC). However, its efficacy is insufficient because of acquired resistance. We investigated the role of exosomal miRNA exchange between resistant cancer cells and naive cancer cells in the development of lenvatinib resistance. Materials and Methods: We generated lenvatinib-resistant (LVT-res) Huh7 and PLC cell lines. We first analyzed the miRNA expression profiles of Nrf2 in cancer using three public datasets and then investigated exosomal miRNA expressions. Exosomal miRNA-132 was found to be elevated in resistant cells compared with parental cells. The parental cells were cocultured with LVT-res cultured conditioned medium as recipient cells. We then compared the characteristics in parental cancer cells, resistant cells, and recipient cells. Results: The proliferation and migration rates of recipient cells were significantly increased compared with the parental cells. Recipient cells also showed chemoresistance. The PTEN/GSK3β/Nrf2 signaling pathway was significantly upregulated in recipient cells compared with the parental cells. Inhibition of exosomal miRNA-132 reduced the malignant potential of recipient cells, chemoresistance, cell proliferation, and migration rates. Furthermore, the PTEN/GSK3β/Nrf2 signaling pathway was downregulated in recipient cells with inhibition of exosomal miRNA-132. Conclusion: Our study provides new findings on the role of the miRNA-132/Nrf2 axis in LVT-res cancer cells. This might be a potential therapeutic target in HCC chemoresistance.

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HCCPTENTME

Identifiers

PMID41488833
PMCPMC12757161

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.