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Exosomal microRNA-23a-3p contributes to the progression of cholangiocarcinoma by interaction with Dynamin3.

ABSTRACT: Cholangiocarcinoma (abbreviated as CCA) accounts for about 3% of digestive tract tumors, which is a rare disease with relatively low incidence. Herein, we firstly discovered overexpression of microRNA-23a-3p (abbreviated as miR-23a-3p) in CCA tissues, as well as cell lines via bioinformatics prediction. Next, by conducting miR-23a-3p knockdown system in HUCCT1 cells and miR-23a-3p overexpression system in RBE cells, we investigated the biological effects of miR-23a-3p. Based on our findings, inhibition of miR-23a-3p was able to prevent cancer cell proliferation via colony formation, CCK-8, as well as EdU assays. Moreover, invasion as well as migration abilities of cells was examined by transwell assay and wound healing test. Animal study further verified that knockdown miR-23a-3p slowed down tumor growth and lung metastasis. In addition, we identified cholangiocarcinoma cells transferred miR-23a-3p through exosomes by a series of assays. Functional experiments have confirmed that exosomal miR-23a-3p could benefit for cancer cell growth and metastasis, serving as a cancer promoting gene. Furthermore, we found Dynamin3 (abbreviated as DNM3) turned out to be a target of miR-23a-3p, while DNM3 was down-regulated in cholangiocarcinoma. Knockdown DNM3 accelerated cancer cell development. Collectively, our findings firstly pointed out that exosomal miR-23a-3p was conducive to the progression of cholangiocarcinoma by interaction with DNM3, which provided potential evidence for cancer treatment.

SUBMITTER: Ni Q

PROVIDER: S-EPMC8973721 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Exosomal microRNA-23a-3p contributes to the progression of cholangiocarcinoma by interaction with Dynamin3.

Ni Qingfeng Q Zhang Hai H Shi Xiaoli X Li Xiangcheng X

Bioengineered 20220301 3

Cholangiocarcinoma (abbreviated as CCA) accounts for about 3% of digestive tract tumors, which is a rare disease with relatively low incidence. Herein, we firstly discovered overexpression of microRNA-23a-3p (abbreviated as miR-23a-3p) in CCA tissues, as well as cell lines via bioinformatics prediction. Next, by conducting miR-23a-3p knockdown system in HUCCT1 cells and miR-23a-3p overexpression system in RBE cells, we investigated the biological effects of miR-23a-3p. Based on our findings, inh ...[more]

PMID: 35200104

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Project description:Background: Osteosarcoma (OS) is the most common primary malignant tumor originating in bone. Immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) participates in tumor immune tolerance and promotes tumor progression, while the study of IDO1 in OS is limited. Methods: Immunohistochemistry analysis was performed to test the expression of IDO1 and Ki67. The relationship between IDO1 or Ki67 positive count and clinical stage of the patient was analyzed. Laboratory test indexes including serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), white blood cell (WBC) count and C-reactive protein (CRP) at diagnosis of OS patients were collected. The relationship between positive count of IDO1 and Ki67 or laboratory test indexes was analyzed by Pearson's correlation analysis. IDO1 stably overexpressed cell lines of these cells (MG63 OE, 143B OE and hFOB1.19 OE) were constructed and validated by Western blot and Elisa. Exosomes were isolated from conditioned culture media of these cells and were identified by Zetaview nanoparticle tracking analyzer. Next-generation sequencing was conducted to identify miRNAs enriched in exosomes. Differentially expressed miRNAs (DE miRNAs) were verified in clinical samples and cell lines by qPCR. Biological processes and cell components analysis of DE miRNAs was conducted by GO enrichment analysis using the protein interaction network database. Results: Immunosuppressive enzyme IDO1 was highly expressed in tumor tissues. 66.7% (6/9) of the tissues showed moderately or strongly positive immunostaining signal of IDO1, and 33.3% (3/9) were weakly positive. The expression of IDO1 was positively related to Ki67 and associated with prognostic-related clinical features of OS patients. Overexpression of IDO1 significantly affected the exosome-derived miRNA subsets from MG63, 143B and hFOB1.19 cells. A total of 1244 DE miRNAs were identified, and hsa-miR-23a-3p was further screened as key DE miRNA involved in the progression of OS. GO analysis of target genes of the DE miRNA results showed that target enrichment in the functions of immune regulation and tumor progression. Discussion: Our results indicate that IDO1 has the potential to promote the progression of OS that is related to miRNAs mediated tumor immunity. Targeting IDO1-mediated hsa-miR-23a-3p may be a potential therapeutic strategy for OS treatment.

Dataset Information

Exosomal microRNA-23a-3p contributes to the progression of cholangiocarcinoma by interaction with Dynamin3.

Publications

Exosomal microRNA-23a-3p contributes to the progression of cholangiocarcinoma by interaction with Dynamin3.

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