癌相关成纤维细胞释放的携带 miR-199a-5p 的细胞外囊泡通过调节 FKBP5 介导的 AKT1/mTORC1 信号通路促进胃癌的进展。
Cancer-associated fibroblast-released extracellular vesicles carrying miR-199a-5p induces the progression of gastric cancer through regulation of FKBP5-mediated AKT1/mTORC1 signaling pathway.
机构信息
Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
Department of Medical Oncology, Tumor Hospital Affiliated to Nantong University & Nantong Tumor Hospital, Nantong, P.R. China.
出版信息
Cell Cycle. 2022 Dec;21(24):2590-2601. doi: 10.1080/15384101.2022.2105092. Epub 2022 Aug 25.
Abstract
Accumulating evidence has unfolded the significance of extracellular vesicles (EVs) in diseases and cancers. Here, we attempted to discuss the role of cancer-associated fibroblasts (CAFs)-derived EVs containing miR-199a-5p in gastric tumorigenesis. Upregulated miR-199a-5p was first identified in cancer cells. Then, we selected CAFs for isolation of EVs which were co-cultured with AGS cells. We observed successful delivery of miR-199a-5p via CAF-derived EVs. Besides, miR-199a-5p promoted malignant properties of AGS cells. Moreover, miR-199a-5p downregulated FKBP5, leading to upregulated phosphorylation level of AKT1, which promoted the malignant phenotypes of AGS cells by activating mammalian target of rapamycin complex 1(mTORC1). Exosomal miR-199a-5p from CAFs promoted gastric tumorigenesis . Our findings point toward the critical role of CAFs-derived EVs carrying miR-199a-5p in gastric cancer progression.
摘要
越来越多的证据揭示了细胞外囊泡（EVs）在疾病和癌症中的重要作用。在这里，我们试图探讨含有 miR-199a-5p 的癌相关成纤维细胞（CAFs）衍生的 EVs 在胃肿瘤发生中的作用。首先在癌细胞中鉴定到上调的 miR-199a-5p。然后，我们选择 CAFs 分离 EVs，并用其与 AGS 细胞共培养。我们观察到 miR-199a-5p 通过 CAF 衍生的 EVs 成功传递。此外，miR-199a-5p 促进了 AGS 细胞的恶性特性。此外，miR-199a-5p 下调 FKBP5，导致 AKT1 的磷酸化水平上调，通过激活雷帕霉素靶蛋白复合物 1（mTORC1）促进 AGS 细胞的恶性表型。来自 CAFs 的外泌体 miR-199a-5p 促进了胃癌的发生。我们的研究结果表明，携带 miR-199a-5p 的 CAFs 衍生 EVs 在胃癌进展中起着关键作用。
相似文献
1
Cancer-associated fibroblast-released extracellular vesicles carrying miR-199a-5p induces the progression of gastric cancer through regulation of FKBP5-mediated AKT1/mTORC1 signaling pathway.癌相关成纤维细胞释放的携带 miR-199a-5p 的细胞外囊泡通过调节 FKBP5 介导的 AKT1/mTORC1 信号通路促进胃癌的进展。
Cell Cycle. 2022 Dec;21(24):2590-2601. doi: 10.1080/15384101.2022.2105092. Epub 2022 Aug 25.
2
Extracellular vesicles-encapsulated microRNA-10a-5p shed from cancer-associated fibroblast facilitates cervical squamous cell carcinoma cell angiogenesis and tumorigenicity via Hedgehog signaling pathway.癌症相关成纤维细胞分泌的细胞外囊泡包裹的微小RNA-10a-5p通过刺猬信号通路促进宫颈鳞状细胞癌细胞血管生成和致瘤性。
Cancer Gene Ther. 2021 May;28(5):529-542. doi: 10.1038/s41417-020-00238-9. Epub 2020 Nov 24.
3
Cancer-associated fibroblasts derived extracellular vesicles promote angiogenesis of colorectal adenocarcinoma cells through miR-135b-5p/FOXO1 axis.癌相关成纤维细胞衍生的细胞外囊泡通过 miR-135b-5p/FOXO1 轴促进结直肠腺癌细胞的血管生成。
Cancer Biol Ther. 2022 Dec 31;23(1):76-88. doi: 10.1080/15384047.2021.2017222.
4
Breast cancer cell-derived extracellular vesicles transfer miR-182-5p and promote breast carcinogenesis via the CMTM7/EGFR/AKT axis.乳腺癌细胞衍生的细胞外囊泡通过 CMTM7/EGFR/AKT 轴转移 miR-182-5p 并促进乳腺癌发生。
Mol Med. 2021 Jul 16;27(1):78. doi: 10.1186/s10020-021-00338-8.
5
Extracellular vesicles derived from cancer-associated fibroblast carries miR-224-5p targeting SLC4A4 to promote the proliferation, invasion and migration of colorectal cancer cells.源自癌症相关成纤维细胞的细胞外囊泡携带 miR-224-5p 靶向 SLC4A4 促进结直肠癌细胞的增殖、侵袭和迁移。
Carcinogenesis. 2021 Oct 5;42(9):1143-1153. doi: 10.1093/carcin/bgab055.
6
MiR-199a-5p-containing macrophage-derived extracellular vesicles inhibit SMARCA4 and alleviate atherosclerosis by reducing endothelial cell pyroptosis.载 miR-199a-5p 的巨噬细胞衍生细胞外囊泡通过减少内皮细胞焦亡来抑制 SMARCA4 并减轻动脉粥样硬化。
Cell Biol Toxicol. 2023 Jun;39(3):591-605. doi: 10.1007/s10565-022-09732-2. Epub 2022 Aug 5.
7
Hypoxic glioma-derived extracellular vesicles harboring MicroRNA-10b-5p enhance M2 polarization of macrophages to promote the development of glioma.缺氧胶质瘤衍生的细胞外囊泡携带 microRNA-10b-5p 增强巨噬细胞 M2 极化，促进胶质瘤的发展。
CNS Neurosci Ther. 2022 Nov;28(11):1733-1747. doi: 10.1111/cns.13905. Epub 2022 Sep 2.
8
CINC-2 and miR-199a-5p in EVs secreted by transplanted Thy1 cells activate hepatocytic progenitor cell growth in rat liver regeneration.移植的 Thy1 细胞分泌的 EVs 中的 CINC-2 和 miR-199a-5p 激活大鼠肝再生中的肝祖细胞生长。
Stem Cell Res Ther. 2023 May 16;14(1):134. doi: 10.1186/s13287-023-03346-z.
9
Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p.癌相关成纤维细胞通过外泌体介导的旁分泌 miR-34a-5p 促进口腔癌细胞的增殖和转移。
EBioMedicine. 2018 Oct;36:209-220. doi: 10.1016/j.ebiom.2018.09.006. Epub 2018 Sep 20.
10
Extracellular vesicles derived from miR-199a-5p-modified adipose-derived mesenchymal stem cells alleviate immune thrombocytopenia by inhibiting T helper 17 differentiation.由 miR-199a-5p 修饰的脂肪间充质干细胞来源的细胞外囊泡通过抑制辅助性 T 细胞 17 分化缓解免疫性血小板减少症。
Lab Invest. 2021 Mar;101(3):318-327. doi: 10.1038/s41374-020-00515-z. Epub 2021 Jan 5.
引用本文的文献
1
Regulatory roles of ncRNAs in gastric cancer progression: a comprehensive insight into key signaling pathways.非编码RNA在胃癌进展中的调控作用：对关键信号通路的全面洞察
Med Oncol. 2025 Jul 1;42(8):309. doi: 10.1007/s12032-025-02828-9.
2
Gastroesophageal circulating tumor cell crosstalk with peripheral immune system guides CTC survival and proliferation.胃食管循环肿瘤细胞与外周免疫系统的相互作用指导循环肿瘤细胞的存活和增殖。
Cell Death Dis. 2025 Mar 29;16(1):223. doi: 10.1038/s41419-025-07530-2.
3
Enhanced fibrotic potential of COL1A1NR4A1 fibroblasts in ischemic heart revealed by transcriptional dynamics heterogeneity analysis at both bulk and single-cell levels.通过整体和单细胞水平的转录动力学异质性分析揭示缺血性心脏中COL1A1NR4A1成纤维细胞增强的纤维化潜能
Front Cardiovasc Med. 2025 Jan 6;11:1460813. doi: 10.3389/fcvm.2024.1460813. eCollection 2024.
4
Role of vascular endothelium and exosomes in cancer progression and therapy (Review).血管内皮和外泌体在癌症进展与治疗中的作用（综述）。
Int J Oncol. 2025 Jan;66(1). doi: 10.3892/ijo.2024.5712. Epub 2024 Dec 5.
5
Extracellular vesicle-packaged miR-4253 secreted by cancer-associated fibroblasts facilitates cell proliferation in gastric cancer by inducing macrophage M2 polarization.肿瘤相关成纤维细胞分泌的含有 miR-4253 的细胞外囊泡通过诱导巨噬细胞 M2 极化促进胃癌细胞增殖。
Cancer Biol Ther. 2024 Dec 31;25(1):2424490. doi: 10.1080/15384047.2024.2424490. Epub 2024 Nov 6.
6
The role of microRNAs in the gastric cancer tumor microenvironment.微小 RNA 在胃癌肿瘤微环境中的作用。
Mol Cancer. 2024 Aug 20;23(1):170. doi: 10.1186/s12943-024-02084-x.
7
Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via exosomes in gastrointestinal tumors.胃肠道肿瘤中癌细胞与癌症相关成纤维细胞通过外泌体进行的细胞间串扰。
Front Oncol. 2024 Feb 23;14:1374742. doi: 10.3389/fonc.2024.1374742. eCollection 2024.
8
Cancer-Associated Fibroblast-Secreted Exosomes Promote Gastric Cancer Cell Migration and Invasion via the IL-32/ESR1 Axis.癌症相关成纤维细胞分泌的外泌体通过IL-32/ESR1轴促进胃癌细胞的迁移和侵袭。
Appl Biochem Biotechnol. 2024 Sep;196(9):6045-6058. doi: 10.1007/s12010-023-04782-6. Epub 2024 Jan 5.
9
piRNAs may regulate expression of candidate genes of esophageal adenocarcinoma.piRNAs可能调控食管腺癌候选基因的表达。
Front Genet. 2022 Nov 30;13:1069637. doi: 10.3389/fgene.2022.1069637. eCollection 2022.
10
Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via extracellular vesicles.癌细胞与癌症相关成纤维细胞之间通过细胞外囊泡进行的细胞间串扰。
Cancer Cell Int. 2022 Nov 24;22(1):367. doi: 10.1186/s12935-022-02784-8.
本文引用的文献
1
Gastric carcinoma: Insights into risk factors, methods of diagnosis, possible lines of management, and the role of primary care.胃癌：对危险因素、诊断方法、可能的治疗方案以及初级保健作用的见解。
J Family Med Prim Care. 2020 Jun 30;9(6):2659-2663. doi: 10.4103/jfmpc.jfmpc_527_20. eCollection 2020 Jun.
2
Gastric cancer: a comprehensive review of current and future treatment strategies.胃癌：当前和未来治疗策略的综合综述。
Cancer Metastasis Rev. 2020 Dec;39(4):1179-1203. doi: 10.1007/s10555-020-09925-3. Epub 2020 Sep 7.
3
Gastric cancer.胃癌。
Lancet. 2020 Aug 29;396(10251):635-648. doi: 10.1016/S0140-6736(20)31288-5.
4
Fentanyl inhibits the progression of gastric cancer through the suppression of MMP-9 via the PI3K/Akt signaling pathway.芬太尼通过PI3K/Akt信号通路抑制基质金属蛋白酶-9（MMP-9），从而抑制胃癌的进展。
Ann Transl Med. 2020 Feb;8(4):118. doi: 10.21037/atm.2019.12.161.
5
Long non-coding RNA LINC00858 exerts a tumor-promoting role in colon cancer via HNF4α and WNK2 regulation.长链非编码 RNA LINC00858 通过 HNF4α 和 WNK2 调控促进结肠癌的发生。
Cell Oncol (Dordr). 2020 Apr;43(2):297-310. doi: 10.1007/s13402-019-00490-8. Epub 2019 Dec 28.
6
Circ_0000267 promotes gastric cancer progression via sponging MiR-503-5p and regulating HMGA2 expression.环状 RNA 0000267 通过海绵吸附 miR-503-5p 并调节 HMGA2 表达促进胃癌进展。
Mol Genet Genomic Med. 2020 Feb;8(2):e1093. doi: 10.1002/mgg3.1093. Epub 2019 Dec 17.
7
HIF1α/miR-520a-3p/AKT1/mTOR Feedback Promotes The Proliferation And Glycolysis Of Gastric Cancer Cells.HIF1α/miR-520a-3p/AKT1/mTOR反馈促进胃癌细胞增殖和糖酵解
Cancer Manag Res. 2019 Dec 2;11:10145-10156. doi: 10.2147/CMAR.S223473. eCollection 2019.
8
Downregulation of NUSAP1 suppresses cell proliferation, migration, and invasion via inhibiting mTORC1 signalling pathway in gastric cancer.NUSAP1 的下调通过抑制胃癌中的 mTORC1 信号通路抑制细胞增殖、迁移和侵袭。
Cell Biochem Funct. 2020 Jan;38(1):28-37. doi: 10.1002/cbf.3444. Epub 2019 Nov 11.
9
Extracellular vesicles as biomarkers and therapeutic targets for cancer.细胞外囊泡作为癌症的生物标志物和治疗靶点。
Am J Physiol Cell Physiol. 2020 Jan 1;318(1):C29-C39. doi: 10.1152/ajpcell.00280.2019. Epub 2019 Nov 6.
10
Downregulation of long noncoding RNA LINC01419 inhibits cell migration, invasion, and tumor growth and promotes autophagy inactivation of the PI3K/Akt1/mTOR pathway in gastric cancer.长链非编码RNA LINC01419的下调抑制胃癌细胞的迁移、侵袭和肿瘤生长，并通过PI3K/Akt1/mTOR通路的自噬失活发挥作用。
Ther Adv Med Oncol. 2019 Sep 24;11:1758835919874651. doi: 10.1177/1758835919874651. eCollection 2019.
Zotero 插件