ArticleCell death & disease2025
Targeting the ROCK2/UBA52/DRP1 axis enhances ferroptosis and overcomes pemigatinib resistance in Cholangiocarcinoma.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- VPS33A Promotes Pemigatinib Resistance in Cholangiocarcinoma via Autophagy.Digestive diseases and sciences · 2026Article
- Review
- Imbalances of mitochondrial dynamics in solid tumors.Oncogenesis · 2026Review
- Article
- Competitive Binding of UBA52 and HOPX Modulates β-catenin Stability in Colorectal Cancer in the Context of High-Iron Intake.International journal of biological sciences · 2026Article
- Targeting ferroptosis and cuproptosis in gastrointestinal cancers: molecular mechanisms, metabolic vulnerabilities, and therapeutic interventions.Molecular biomedicine · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholangiocarcinoma (CCA) is a highly aggressive cancer that arises from the bile duct and has an extremely poor prognosis. Pemigatinib is the only Food and Drug Administration (FDA)-approved CCA-targeted drug. The CCA treatment options are insufficient considering its poor prognosis and increasing morbidity. Recently, Rho-associated coiled-coil containing protein kinase 2 (ROCK2) has been reported to promote resistance to chemotherapy. In this study, we investigated the role that ROCK2 plays in the development of resistance of CCA cells to Pemigatinib. Here, we developed Pemigatinib-resistant CCA cells, performed mRNA sequencing, retrieved The Cancer Genome Atlas (TCGA) data, and analysed ROCK2 expression in a large CCA cohort. The expression level of ROCK2 in CCA cells was significantly higher than that in adjacent noncancerous tissues. Increased expression of ROCK2 in CCA was related to a late TNM stage and decreased overall survival. Functional experiments revealed that downregulating the expression of ROCK2 promotes the ferroptosis of CCA cells, and enhances sensitivity to Pemigatinib. Moreover, upregulation of ROCK2 increased the expression of Drp1 protein. The effect of downregulating ROCK2 was reversed by Drp1 overexpression, and Drp1 knockdown inhibited Ferroptosis driven by ROCK2 overexpression. Mechanistically, ROCK2 stabilized the expression of Drp1 by competing with UBA52 to bind Drp1 and inhibiting the ubiquitination-mediated degradation of Drp1. Blocking of the UBA52- Drp1 axis inhibited the antitumour effect of Pemigatinib in ROCK2-knockdown cells both in vitro and in vivo. In conclusion, the ROCK2/UBA52/Drp1 axis is a pivotal driver of Pemigatinib resistance in CCA cells. These results provide novel insights into Pemigatinib resistance in CCA cells, suggesting that ROCK2 is a promising therapeutic target for the treatment of CCA.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.