2. Academic Validation
  3. Tumor-Associated Fibroblast-Derived Exosomal circDennd1b Promotes Pituitary Adenoma Progression by Modulating the miR-145-5p/ONECUT2 Axis and Activating the MAPK Pathway

Tumor-Associated Fibroblast-Derived Exosomal circDennd1b Promotes Pituitary Adenoma Progression by Modulating the miR-145-5p/ONECUT2 Axis and Activating the MAPK Pathway

  • Cancers (Basel). 2023 Jun 27;15(13):3375. doi: 10.3390/cancers15133375.
Qian Jiang 1 2,  Zhuowei Lei 3,  Zihan Wang 1 2,  Quanji Wang 1 2,  Zhuo Zhang 1 2,  Xiaojin Liu 1 2,  Biao Xing 1 2,  Sihan Li 1 2,  Xiang Guo 1 2,  Yanchao Liu 1 2,  Xingbo Li 1 2,  Yiwei Qi 1 2,  Kai Shu 1,  Huaqiu Zhang 1 2,  Yimin Huang 1 2,  Ting Lei 1 2
Affiliations

Affiliations

  • 1 Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China.
  • 2 Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 3 Department of Orthopedics, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan 430030, China.
PMID: 37444485 DOI: 10.3390/cancers15133375
Abstract

TAF participated in the progression of various cancers, including PA via the release of soluble factors. Exosomes belonged to extracellular vesicles, which were revealed as a crucial participator in intercellular communication. However, the expression pattern and effect of TAF-derived exosomes remained largely unknown in PA. In the present study, we performed in silico analysis based on public RNA-seq datasets to generate the circRNA/miRNA regulatory network. The qRT-PCR, Western blotting, RNA pull-down, and luciferase assay were performed to investigate the effect of TAF-derived exosomes. TAF-derived exosomal circDennd1b was significantly upregulated in PA and promoted the proliferation, migration, and invasion of PA cells via sponging miR-145-5p in PA cells. In addition, miR-145-5p directly regulated One Cut homeobox 2 (ONECUT2/OC2) expression and inhibited the promoting effect of ONECUT2 on PA. We further demonstrated that ONECUT2 transcriptionally increased Fibroblast Growth Factor receptor 3 (FGFR3) expression, which further activates the mitogen-activated protein kinases (MAPK) pathway, thus promoting PA progression. Moreover, the suppression of TAFs by ABT-263 and ONECUT2 by CSRM617 inhibited the growth of PA. In conclusion, our study illustrated that TAF-derived exosomal circDennd1b affected PA progression via regulating ONECUT2 expression, which provides a potential therapeutic strategy against aggressive PA.

Keywords

FGFR3; ONECUT2; circDennd1b; exosome; miR-145-5p; pituitary adenoma; tumor-associated fibroblasts.

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