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Int J Biol Sci 2023; 19(14):4571-4587. doi:10.7150/ijbs.83170 This issue Cite

Research Paper

Exosomal miR-30a-5p promoted intrahepatic cholangiocarcinoma progression by increasing angiogenesis and vascular permeability in PDCD10 dependent manner

Wangjie Jiang1,2*, Xiaoli Shi1,2,3*, Lizhu Sun4*, Yaodong Zhang1,2, Xiangxu Kong1,2, Xiao Yang1,2, Yongmei Yin4✉, Changxian Li1,2✉, Xiangcheng Li1,2✉

1. Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
2. Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu Province, China.
3. School of Medicine, Southeast University, Nanjing, Jiangsu Province, China.
4. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
* These authors contributed equally to this work.

✉ Corresponding author: Xiangcheng Li. Telephone:86+18951999088; Fax: 86-25-6830-3226; E-mail: drxcliedu.cn. Changxian Li. Telephone:86+18761854602; Fax: 86-25-6830-3226; E-mail: doclicx20com. Yongmei Yin. Telephone:86+15851859552; Fax: 86- More

Citation:
Jiang W, Shi X, Sun L, Zhang Y, Kong X, Yang X, Yin Y, Li C, Li X. Exosomal miR-30a-5p promoted intrahepatic cholangiocarcinoma progression by increasing angiogenesis and vascular permeability in PDCD10 dependent manner. Int J Biol Sci 2023; 19(14):4571-4587. doi:10.7150/ijbs.83170. https://www.ijbs.com/v19p4571.htm
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Abstract

Graphic abstract

Tumor-associated angiogenesis positively associates with malignant metastasis of intrahepatic cholangiocarcinoma (ICCA). Cancer cell-derived exosomes carrying microRNAs involves in tumor microenvironment (TME) regulation. We aimed to evaluate exosomal miR-30a-5p in ICCA development. Our data showed that increased miR-30a-5p level was correlated with higher microvascular density (MVD) and worse prognosis. Augmented miR-30a-5p expression was induced by hypoxia induced factor 1α (HIF-1α) in ICCA cell. Further exploration revealed that ICCA-derived miR-30a-5p could be transferred to endothelial and increased endothelial cells recruitment and proliferation, induced angiogenesis and vascular permeability in exosome dependent manner. In addition, circulating exosomal miR-30a-5p was higher in ICCA patients, and correlated with ICCA tissues-expressing miR-30a-5p. Hypoxic stress enhanced the effects of exosomal miR-30a-5p on endothelial-associated phenotypes. Rescued experiments showed that exosomal miR-30a-5p modulated endothelial-associated phenotypes in a way relied on programmed cell death 10 (PDCD10). Moreover, we revealed that the packing of miR-30a-5p into ICCA cells-derived exosomes was mediated by eukaryotic translation initiation factor 4B (EIF4B). More importantly, the combined application of targeting miR-30a-5p and apatinib could synergistically improve antiangiogenic efficacy in ICCA. Combined, ICCA-derived exosomal miR-30a-5p could be an excellent therapeutic and monitoring indicator for ICCA patients.

Keywords: cholangiocarcinoma, miR-30a-5p, PDCD10, angiogenesis, permeability

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APA
Jiang, W., Shi, X., Sun, L., Zhang, Y., Kong, X., Yang, X., Yin, Y., Li, C., Li, X. (2023). Exosomal miR-30a-5p promoted intrahepatic cholangiocarcinoma progression by increasing angiogenesis and vascular permeability in PDCD10 dependent manner. International Journal of Biological Sciences, 19(14), 4571-4587. https://doi.org/10.7150/ijbs.83170.

ACS
Jiang, W.; Shi, X.; Sun, L.; Zhang, Y.; Kong, X.; Yang, X.; Yin, Y.; Li, C.; Li, X. Exosomal miR-30a-5p promoted intrahepatic cholangiocarcinoma progression by increasing angiogenesis and vascular permeability in PDCD10 dependent manner. Int. J. Biol. Sci. 2023, 19 (14), 4571-4587. DOI: 10.7150/ijbs.83170.

NLM
Jiang W, Shi X, Sun L, Zhang Y, Kong X, Yang X, Yin Y, Li C, Li X. Exosomal miR-30a-5p promoted intrahepatic cholangiocarcinoma progression by increasing angiogenesis and vascular permeability in PDCD10 dependent manner. Int J Biol Sci 2023; 19(14):4571-4587. doi:10.7150/ijbs.83170. https://www.ijbs.com/v19p4571.htm

CSE
Jiang W, Shi X, Sun L, Zhang Y, Kong X, Yang X, Yin Y, Li C, Li X. 2023. Exosomal miR-30a-5p promoted intrahepatic cholangiocarcinoma progression by increasing angiogenesis and vascular permeability in PDCD10 dependent manner. Int J Biol Sci. 19(14):4571-4587.

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