2. Academic Validation
  3. Cancer-Associated fibroblasts regulate the development of cholangiocarcinoma through IL-6/STAT3/AKR1C3 signaling axis

Cancer-Associated fibroblasts regulate the development of cholangiocarcinoma through IL-6/STAT3/AKR1C3 signaling axis

  • Sci Rep. 2026 Feb 25;16(1):10467. doi: 10.1038/s41598-026-37583-y.
Tian-Cong Huang # 1 2,  Wen-du Feng # 1,  Guo-Xu Fang # 3 4,  Qing-Hua Zhang 2,  Guang-Ya Wei 2,  Cheng-Zong Li 1,  Jian-Min Wang 5 6,  Jing-Feng Liu 7 8 9 10
Affiliations

Affiliations

  • 1 Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China.
  • 2 Clinical Oncology School, Fujian Medical University, Fuzhou, 350108, China.
  • 3 Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China.
  • 4 The Big Data Institute of Southeast Hepatobiliary Health Information, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China.
  • 5 Innovation center for cancer research, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350108, China. [email protected].
  • 6 Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fujian Cancer Hospital, Fuzhou, 350108, China. [email protected].
  • 7 The Big Data Institute of Southeast Hepatobiliary Health Information, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China. [email protected].
  • 8 Department of Hepatopancreatobiliary Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350108, China. [email protected].
  • 9 Innovation center for cancer research, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350108, China. [email protected].
  • 10 Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fujian Cancer Hospital, Fuzhou, 350108, China. [email protected].
  • # Contributed equally.
PMID: 41735359 DOI: 10.1038/s41598-026-37583-y
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.

Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-37583-y.

Keywords

AKR1C3; Cancer-associated fibroblasts; Cholangiocarcinoma; IL-6/STAT3 signaling; Oncogene..

Figures
Products