miR-4510 acts as a tumor suppressor in gastrointestinal stromal tumor by targeting APOC2.


Journal

Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222

Informations de publication

Date de publication:
07 2020
Historique:
received: 17 07 2019
accepted: 09 01 2020
pubmed: 25 1 2020
medline: 11 3 2021
entrez: 25 1 2020
Statut: ppublish

Résumé

Dysregulation of microRNAs (miRNAs) expression has been demonstrated in gastrointestinal stromal tumor (GIST). In this study, we aimed to determine the differential miRNAs expression in GISTs and explore the functional mechanism of differential miRNAs in GIST cells. We measured differential miRNAs in six pairs of GIST tissues and matched adjacent tissues through a high-throughput sequencing, which was confirmed in 64 pairs of GIST tissues and adjacent tissues by real-time polymerase chain reaction. We found that miR-4510 expression was significantly downregulated in GIST tissues compared to matched control tissues. Luciferase reporter assay identified apolipoprotein C-II (APOC2) as a direct target of miR-4510. Overexpression of miR-4510 inhibited the mRNA and protein expression of APOC2. In addition, overexpression of miR-4510 suppressed GIST cell proliferation, migration, and invasion. Overexpression of miR-4510 also inhibited the phosphorylation of AKT and ERK1/2, reduced the expression of matrix metallopeptidase 2 (MMP2) and MMP9. APOC2 knockdown mimicked the effect of miR-4510 overexpression. Further investigation confirmed that APOC2 was notably upregulated in GIST tissues compared to adjacent control tissues. These results suggested that miR-4510 downregulation could promote GIST progression, including growth, invasion, and metastasis, through increasing APOC2 expression.

Identifiants

pubmed: 31975384
doi: 10.1002/jcp.29506
doi:

Substances chimiques

Apolipoprotein C-II 0
MicroRNAs 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5711-5721

Informations de copyright

© 2020 Wiley Periodicals, Inc.

Références

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Auteurs

Yuan Chen (Y)

Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Chengkun Qin (C)

Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Xianping Cui (X)

Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Wenmao Geng (W)

Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Guozhe Xian (G)

Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Zhiyi Wang (Z)

Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

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