PMID- 32695810 OWN - NLM STAT- MEDLINE DCOM- 20210416 LR - 20210416 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2020 DP - 2020 TI - OSCC Exosomes Regulate miR-210-3p Targeting EFNA3 to Promote Oral Cancer Angiogenesis through the PI3K/AKT Pathway. PG - 2125656 LID - 10.1155/2020/2125656 [doi] LID - 2125656 AB - This study is aimed at determining how oral squamous cell carcinoma (OSCC) regulates the angiogenesis of HUVECs through miR-210-3p expression and exploring the relationship among miR-210-3p, its target protein, and the possible mechanism of angiogenesis regulation. miR-210-3p expression was detected in OSCC tissues and juxta cancerous tissues (JCT), and the relationship among miR-210-3p, microvessel density (MVD), and histopathologic features was analyzed. A conditioned medium (CM) of the OSCC cell line CAL27 was collected to stimulate human umbilical vein endothelial cells (HUVECs), and the miR-210-3p levels and tube formation capability of HUVECs were measured. The target protein level of miR-210-3p was altered; then, PI3K/AKT pathway activation in HUVECs was detected. miR-210-3p was tested in exosomes separated from CAL27 CM, and the transfer of miR-210-3p from OSCC exosomes to HUVECs was verified. Then, we found that the OSCC tissues had higher miR-210-3p levels than the JCT, and miR-210-3p level was positively correlated with MVD and tumor grade. CAL27 CM was able to elevate miR-210-3p levels in HUVECs and promoted tube formation. EFNA3 was the target gene of miR-210-3p, and ephrinA3 protein level was able to influence the migration and proliferation of HUVECs. The levels of phosphorylated AKT in the HUVECs increased when ephrinA3 was downregulated, and the upregulation of ephrinA3 resulted in the suppression of the PI3K/AKT pathway. miR-210-3p was detected in exosomes isolated from the CM of CAL27 cells, and miR-210-3p level in the HUVECs was elevated after absorbing the OSCC exosomes. In conclusion, miR-210-3p was more overexpressed in OSCC tissues than in the JCT. The exosomes secreted by OSCC cells were able to upregulate miR-210-3p expression and reduce ephrinA3 expression in HUVECs and promoted tube formation through the PI3K/AKT signaling pathway. CI - Copyright (c) 2020 Hui Wang et al. FAU - Wang, Hui AU - Wang H AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China. FAU - Wang, Lin AU - Wang L AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China. FAU - Zhou, Xiaocheng AU - Zhou X AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China. FAU - Luo, Xinyue AU - Luo X AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China. FAU - Liu, Ke AU - Liu K AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China. FAU - Jiang, Erhui AU - Jiang E AUID- ORCID: 0000-0003-4668-026X AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China. FAU - Chen, Yang AU - Chen Y AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China. FAU - Shao, Zhe AU - Shao Z AUID- ORCID: 0000-0003-2357-3760 AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China. FAU - Shang, Zhengjun AU - Shang Z AUID- ORCID: 0000-0002-4884-8129 AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China. LA - eng PT - Journal Article DEP - 20200708 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (Culture Media, Conditioned) RN - 0 (Ephrin-A3) RN - 0 (MIRN210 microRNA, human) RN - 0 (MicroRNAs) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Base Sequence MH - Carcinoma, Squamous Cell/*genetics/pathology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Culture Media, Conditioned/pharmacology MH - Ephrin-A3/genetics/*metabolism MH - Exosomes/*metabolism MH - Gene Expression Regulation, Neoplastic/drug effects MH - Human Umbilical Vein Endothelial Cells/drug effects/metabolism MH - Humans MH - MicroRNAs/genetics/*metabolism MH - Microvessels/pathology MH - Mouth Neoplasms/*genetics/pathology MH - Neovascularization, Pathologic/*genetics MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Signal Transduction MH - Up-Regulation/drug effects PMC - PMC7368228 COIS- The authors declare that there is no conflict of interest regarding the publication of this paper. EDAT- 2020/07/23 06:00 MHDA- 2021/04/17 06:00 PMCR- 2020/07/08 CRDT- 2020/07/23 06:00 PHST- 2020/03/01 00:00 [received] PHST- 2020/06/19 00:00 [accepted] PHST- 2020/07/23 06:00 [entrez] PHST- 2020/07/23 06:00 [pubmed] PHST- 2021/04/17 06:00 [medline] PHST- 2020/07/08 00:00 [pmc-release] AID - 10.1155/2020/2125656 [doi] PST - epublish SO - Biomed Res Int. 2020 Jul 8;2020:2125656. doi: 10.1155/2020/2125656. eCollection 2020.