Mechanism of knocking down nuclear factor I-C derived exosomespromoting metastasis of endometrial cancer cells

doi:10.16098/j.issn.0529-1356.2026.06.011

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Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (5) : 591-601. DOI: 10.16098/j.issn.0529-1356.2026.06.011

Cancer Biology

Mechanism of knocking down nuclear factor I-C derived exosomespromoting metastasis of endometrial cancer cells

LI Yuan¹, TAN Jie-wen², XIN Lu ¹, QIAN Yu-jia2, XIE Wen-yi², GAO Tan-ji-qiao³, BIAN Jin-yan², LIU Chao¹, ZHANG Jing^1*

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Abstract

Objective To explore the role of nuclear factor I-C (NFIC) in pre-metastatic niche formation and matastasis in endometrial cancer (EC). Methods NFIC small interfering RNA (siRNA) and overexpression plasmid were transfected into Ishikawa cells respectively to investigate the effect of NFIC on cell migration and invasion through wound healing and Transwell invasion assays. Exosomes derived from NFIC knockdown cells were extracted to investigate the effect on the migration and invasion of Ishikawa cells, observe whether these exosomes could increase endothelial cell permeability in vivo and in vitro, address the effect of pre-injection of these exosomes on the metastasis of Ishikawa cells, and explore the underlying mechanism by small RNA sequencing. Results NFIC knockdown increased the migration and invasion of Ishikawa cells. Exosomes from NFIC knockdown cells increased the migration and invasion of Ishikawa cells, and promoted the metastasis of Ishikawa cells in murine models by destroying barrier function of endothelial monolayer. Furthermore, micro RNA(miR)-4739 level elevated significantly in exosomes from NFIC knockdown cells, and the exosome mediated transfer of miR-4739 could downregulate the expression of syndecan-4（SDC4）, then caused the impairment of endothelial barrier. Conclusion NFIC deficiency in EC cells promotes the formation of pre-metastatic niche through exosome mediated transfer of miR-4739, which downregulates the expression of SDC4 to induce vascular endothelial disruption.

Key words

Nuclear factor I-C

/ Endometrial cancer / Metastasis / Exosome / Nude mouse tumor metastasis model / Small RNA sequencing / Vascular endothelial cell

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LI Yuan, TAN Jie-wen, XIN Lu , QIAN Yu-jia, XIE Wen-yi, GAO Tan-ji-qiao, BIAN Jin-yan, LIU Chao, ZHANG Jing. Mechanism of knocking down nuclear factor I-C derived exosomespromoting metastasis of endometrial cancer cells[J]. Acta Anatomica Sinica. 2026, 57(5): 591-601 https://doi.org/10.16098/j.issn.0529-1356.2026.06.011

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