Abstract
Cancer-associated fibroblasts (CAFs) are the dominant component of the tumor microenvironment (TME), which contributes to tumor progression. Aldo-keto reductase 1 family member C3 (AKR1C3) has been correlated with the development of various kinds of cancers. Nevertheless, the effect and mechanism of CAFs on AKR1C3 in cholangiocarcinoma (CCA) remain unelucidated. Q-PCR assay and IHC were conducted to detect the expression of AKR1C3 in CCA tissues. Subsequently, CCK8 assay, colony formation, crystal violet assay, apoptosis assay, glucose uptake, and lactate production assay were performed to investigate the effect of AKR1C3 on the biological function of CCA cells. The regulatory effect of CAFs on AKR1C3 was examined in CCA cells cultured with a CAF-conditioned medium. Finally, western blot, co-immunoprecipitation, and ubiquitination degradation kits were used to explore the potential molecular mechanism. AKR1C3 was overexpressed in CCA tissues compared to normal tissues. Patients with a high staining intensity score of AKR1C3 exhibited a poor overall survival time. AKR1C3 was found to enhance the proliferation, colony formation, drug resistance, and aerobic glycolysis of CCA cells. Moreover, CAFs modulate the overexpression of AKR1C3 in the onset and progression of CCA through the IL-6/STAT3 signaling pathway. This regulation occurs via the IL-6/STAT3/AKR1C3 signaling axis, indicating that targeting AKR1C3 could serve as a potential therapeutic strategy for patients with CCA.
Data availability
Raw data are available upon request to the corresponding author.
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Acknowledgements
This work was supported by the Natural Science Foundation of Fujian Province (Grant Number: 2022J01776).
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Tian-cong Huang and Wen-du Feng conceived the study; Guo-xu Fang, Qing-hua Zhang, Guang-ya Wei and Cheng-zong Li collected the report; Tian-cong Huang, Jian-min Wang and Jing-Feng Liu wrote the manuscript and edited the manuscript. All authors have approved publishment of the manuscript.
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Huang, Tc., Feng, Wd., Fang, Gx. et al. Cancer-Associated fibroblasts regulate the development of cholangiocarcinoma through IL-6/STAT3/AKR1C3 signaling axis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37583-y
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DOI: https://doi.org/10.1038/s41598-026-37583-y
