Exosomal miR-320d promotes angiogenesis and colorectal cancer metastasis via targeting GNAI1 to affect the JAK2/STAT3 signaling pathway

被引：1

作者：

Wu, Yawen ^{[1
,2
]}

Zhang, Jie ^{[1
]}

Li, Guanghao ^{[1
]}

Wang, Li ^{[3
]}

Zhao, Yajing ^{[4
]}

Zheng, Baibing ^{[5
]}

Lin, Fanfeng ^{[1
]}

Xie, Li ^{[1
]}

机构：

[1] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Shandong Prov Key Lab Precis Oncol, Jinan, Shandong, Peoples R China

[2] Shandong Univ, Childrens Hosp, Clin Lab, Jinan, Shandong, Peoples R China

[3] Hangzhou Fuyang Dist First Peoples Hosp, Dept Clin Lab, Hangzhou, Zhejiang, Peoples R China

[4] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Dept Clin Lab, Jinan, Shandong, Peoples R China

[5] Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjins Clin Res Ctr Canc,Dept Lab, Tianjin, Peoples R China

来源：

CELL DEATH & DISEASE | 2024年 / 15卷 / 12期

关键词：

GROWTH;

D O I：

10.1038/s41419-024-07297-y

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Colorectal cancer is a common malignant tumor, whose growth and metastasis are influenced by numerous factors. MicroRNAs have garnered increasing attention in recent years due to their involvement in tumor development. Exosomes are involved in intercellular signaling and influence tumor development by promoting tumor cell proliferation and metastasis through activation of angiogenesis and other mechanisms. This study aimed to investigate how the exosomes containing miR-320d from colorectal cancer (CRC) cells promote colorectal cancer metastasis by regulating angiogenesis. CRC-derived exosomes containing miR-320d can be transferred to vascular endothelial cells, facilitating their proliferation, invasion, migration, and angiogenesis. By targeting GNAI1, miR-320d in these exosomes reduces GNAI1 levels in endothelial cells, causing more JAK2/STAT3 activation and VEGFA production. This ultimately enhances the migration and angiogenic capacity of vascular endothelial cells. Moreover, CRC patients with high levels of miR-320d in their blood respond better to treatment with bevacizumab. In vivo experiments further proved the role of miR-320d from CRC exosomes in increasing tumor size, blood vessel formation, and the spread of cancer to the liver. In this study, we have demonstrated that exosomal miR-320d promotes cancer cell metastasis and enhances angiogenesis by downregulating GNAI1 expression and enhancing JAK2/STAT3.

引用

页数：14

共 25 条

[1] Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Et al., Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J Clin, 71, pp. 209-249, (2021)
[2] Fane M.E., Ecker B.L., Kaur A., Marino G.E., Alicea G.M., Douglass S.M., Et al., sFRP2 supersedes VEGF as an age-related driver of angiogenesis in melanoma, affecting response to anti-VEGF therapy in older patients, Clin Cancer Res, 26, pp. 5709-5719, (2020)
[3] Zahalka A.H., Frenette P.S., Nerves in cancer, Nat Rev Cancer, 20, pp. 143-157, (2020)
[4] Zhang Y., Cai S., Jia Y., Qi C., Sun J., Zhang H., Et al., Decoding noncoding RNAs: role of microRNAs and long noncoding RNAs in ocular neovascularization, Theranostics, 7, pp. 3155-3167, (2017)
[5] Cao Y., Langer R., Ferrara N., Targeting angiogenesis in oncology, ophthalmology and beyond, Nat Rev Drug Discov, 22, pp. 476-495, (2023)
[6] Zhu L., Sun H.T., Wang S., Huang S.L., Zheng Y., Wang C.Q., Et al., Isolation and characterization of exosomes for cancer research, J Hematol Oncol, 13, (2020)
[7] Chen C., Liu Y., Liu L., Si C., Xu Y., Wu X., Et al., Exosomal circTUBGCP4 promotes vascular endothelial cell tipping and colorectal cancer metastasis by activating Akt signaling pathway, J Exp Clin Cancer Res, 42, (2023)
[8] Xu Z., Chen Y., Ma L., Chen Y., Liu J., Guo Y., Et al., Role of exosomal non-coding RNAs from tumor cells and tumor-associated macrophages in the tumor microenvironment, Mol Ther, 30, pp. 3133-3154, (2022)
[9] Zhang T., Wu Y.C., Mullane P., Ji Y.J., Liu H., He L., Et al., FUS regulates activity of microRNA-mediated gene silencing, Mol Cell, 69, pp. 787-801.e8, (2018)
[10] Sun Z., Shi K., Yang S., Liu J., Zhou Q., Wang G., Et al., Effect of exosomal miRNA on cancer biology and clinical applications, Mol Cancer, 17, (2018)

← 1 2 3 →