MiR-148a inhibits the proliferation and migration of glioblastoma by targeting ITGA9
Glioblastoma is a common malignant primary intracranial tumor characterized by rapid invasive growth and a high recurrence rate after surgery. MicroRNAs (miRNAs) are involved in cell proliferation, differentiation, and apoptosis, and abnormal miRNA expression is associated with the occurrence and progression of various tumors, including glioblastomas. The aim of this study was to determine the levels of miR-148a and integrin subunit alpha 9 (ITGA9) in glioblastoma tissues and cells and their involvement in cancer cell proliferation and migration. Glioblastoma tissues from 19 patients and two glioblastoma cell lines (U87 and LN229) were used in this study. The effects of miR-148a on cell viability, proliferation, colony formation, migration, and invasion were assessed. Glioblastomas were xenografted in nude mice to examine the effects of miR-148a overexpression on tumor growth in vivo. Levels of ITGA9 mRNA and protein in glioblastoma tissues were detected by quantitative reverse transcription PCR and western blot analysis, respectively. The interaction between miR-148a and ITGA9 was determined by a dual-luciferase reporter gene assay. We found that the overexpression of miR-148a decreases the proliferation, clustering, migration, and invasiveness of U87 and LN229 cells and inhibits the tumorigenicity of xenografted glioblastomas. We confirmed that ITGA9 is the target of miR-148a. Restoration of ITGA9 expression reversed the decreased viability, migration, and invasiveness of glioblastoma cells induced by miR-148a overexpression. Our findings indicate that miR-148a can suppress the malignant phenotype of glioblastoma by targeting ITGA9 and identify ITGA9 as a potential therapeutic target for glioblastoma.
KeywordsmiR-148a ITGA9 Glioblastoma Malignant Proliferation Migration
Integrin subunit alpha 9
Cell Counting Kit 8
Reverse-transcription polymerase chain reaction
Three prime untranslated region
We would also like to thank Editage for editing our manuscript.
YW and XG-M designed the research. XT-J and QP performed the experiments, analyzed the data, and wrote the paper. ZY-B performed the cell culture experiments. YS-Y collected the data and performed the statistical analyses.
This work was supported by the Shandong Provincial Natural Science Foundation, China (Grant No. ZR2015HM015) and the Science and Technology Development Plan Project of Jinan City (Grant No. 201302038). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethics approval and consent to participate
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Shandong Provincial Hospital, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of Shandong University.
Informed consent was obtained from all individual participants included in the study.
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