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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
miR-338-3p suppresses neuroblastoma proliferation, invasion and migration through targeting PREX2a
1Department of Pediatric Surgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, China.
Abstract:
MicroRNAs (miRNA) can regulate cancer cell proliferation and metastasis. Here, we show that miR-338-3p is down-regulated in metastatic tumor tissues compared to primary tumors, and that that miR-338-3p can inhibit cell proliferation by inducing cell cycle arrest, as well as restrain cell migration and invasion. PREX2a is confirmed as a direct target of miR-338-3p. Knockdown of PREX2a inhibits cell proliferation, migration and invasion through the PTEN/Akt pathway. miR-338-3p-dependent inhibition of proliferation and invasion can be rescued by PREXa. Overall, this study demonstrates that miR-338-3p affects the PTEN/Akt pathway by down-regulating PREX2a. This newly identified function of miR-338-3p provides novel insights into neuroblastoma and may foster therapeutic applications.
Insights
MicroRNA 338-3p (miR-338-3p) inhibits neuroblastoma growth and spread by targeting PREX2a. This finding reveals a new therapeutic target for neuroblastoma treatment.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are crucial regulators of cancer cell proliferation and metastasis.
- Dysregulation of specific miRNAs is implicated in various cancers, including neuroblastoma.
Purpose of the Study:
- To investigate the role of miR-338-3p in neuroblastoma.
- To identify the molecular targets and pathways regulated by miR-338-3p in cancer progression.
Main Methods:
- Quantitative analysis of miR-338-3p expression in primary and metastatic neuroblastoma tissues.
- In vitro assays to assess the effects of miR-338-3p on cell proliferation, cell cycle, migration, and invasion.
- Identification and validation of PREX2a as a direct target of miR-338-3p.
- Western blot analysis to examine the PTEN/Akt signaling pathway.
Main Results:
- miR-338-3p was significantly down-regulated in metastatic neuroblastoma tissues compared to primary tumors.
- Overexpression of miR-338-3p inhibited neuroblastoma cell proliferation, induced cell cycle arrest, and suppressed cell migration and invasion.
- PREX2a was identified as a direct target of miR-338-3p, and its knockdown mimicked the effects of miR-338-3p.
- miR-338-3p suppressed the PTEN/Akt pathway by down-regulating PREX2a, and this effect was reversed by PREX2a overexpression.
Conclusions:
- miR-338-3p acts as a tumor suppressor in neuroblastoma by inhibiting proliferation and metastasis.
- The miR-338-3p/PREX2a axis regulates the PTEN/Akt pathway, offering a potential therapeutic target for neuroblastoma.
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