MicroRNA-21 overexpression contributes to vestibular schwannoma cell proliferation and survival

Joseph A Cioffi; Wei Ying Yue; Sabrina Mendolia-Loffredo; Kameron R Hansen; P Ashley Wackym; Marlan R Hansen

doi:10.1097/MAO.0b013e3181f20655

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MicroRNA-21 overexpression contributes to vestibular schwannoma cell proliferation and survival

Journal article

Peer reviewed

MicroRNA-21 overexpression contributes to vestibular schwannoma cell proliferation and survival

Joseph A Cioffi, Wei Ying Yue, Sabrina Mendolia-Loffredo, Kameron R Hansen, P Ashley Wackym and Marlan R Hansen

Otology & neurotology, Vol.31(9), pp.1455-1462

12/2010

DOI: 10.1097/MAO.0b013e3181f20655

PMCID: PMC2978772

PMID: 20856158

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url

https://www.ncbi.nlm.nih.gov/pmc/articles/2978772View

Open Access

Abstract

Elevated levels of hsa-microRNA-21 (miR-21) in vestibular schwannomas (VSs) may contribute to tumor growth by downregulating the tumor suppressor phosphatase and tensin homolog (PTEN) and consequent hyperactivation of protein kinase B (AKT), a key signaling protein in the cellular pathways that lead to tumor growth. Vestibular schwannomas are benign tumors that arise from the vestibular nerve. Left untreated, VSs can result in hearing loss, tinnitus, vestibular dysfunction, trigeminal nerve dysfunction, and can even become life threatening. Despite efforts to characterize the VS transcriptome, the molecular pathways that lead to tumorigenesis are not completely understood. MicroRNAs are small RNA molecules that regulate gene expression posttranscriptionally by blocking the production of specific target proteins. We examined miR-21 expression in VSs. To determine the functional significance of miR-21 expression in VS cells, we transfected primary human VS cultures with anti-miR-21 or control, scrambled oligonucleotides. We found consistent overexpression of miR-21 when compared with normal vestibular nerve tissue. Furthermore, elevated levels of miR-21 correlated with decreased levels of PTEN, a known molecular target of miR-21. Anti-miR-21 decreased VS cell proliferation in response to platelet-derived growth factor stimulation and increased apoptosis, suggesting that increased miR-21 levels contributes to VS growth. Because PTEN regulates signaling through the growth-promoting phosphoinositide 3-kinase/AKT pathway, our findings suggest that miR-21 may be a suitable molecular target for therapies aimed specifically at reducing VS growth.

Immunohistochemistry

Cell Proliferation

Humans

Apoptosis - genetics

Gene Knockdown Techniques

RNA, Messenger - biosynthesis

Transfection

Cranial Nerve Neoplasms - genetics

Cell Survival

Electrophoresis, Polyacrylamide Gel

RNA, Messenger - genetics

Cells, Cultured

PTEN Phosphohydrolase - biosynthesis

MicroRNAs - biosynthesis

Neurofibromatosis 2 - genetics

Reverse Transcriptase Polymerase Chain Reaction

Blotting, Western

Neurofibromatosis 2 - pathology

RNA, Neoplasm - biosynthesis

Cranial Nerve Neoplasms - pathology

Neuroma, Acoustic - genetics

RNA, Neoplasm - genetics

Neuroma, Acoustic - pathology

MicroRNAs - genetics

Vestibulocochlear Nerve - pathology

Details

Title: Subtitle: MicroRNA-21 overexpression contributes to vestibular schwannoma cell proliferation and survival
Creators: Joseph A Cioffi - Legacy Clinical Research and Technology Center, Portland, Oregon 97232, USA. joeciof@aol.com
Wei Ying Yue
Sabrina Mendolia-Loffredo
Kameron R Hansen
P Ashley Wackym
Marlan R Hansen
Resource Type: Journal article
Publication Details: Otology & neurotology, Vol.31(9), pp.1455-1462
DOI: 10.1097/MAO.0b013e3181f20655
PMID: 20856158
PMCID: PMC2978772
NLM abbreviation: Otol Neurotol
ISSN: 1531-7129
eISSN: 1537-4505
Publisher: United States
Grant note: R01 DC002971-14 / NIDCD NIH HHS R01 DC009801-03 / NIDCD NIH HHS R01 DC009801 / NIDCD NIH HHS K08DC006211 / NIDCD NIH HHS K08 DC006211 / NIDCD NIH HHS R01 DC002971 / NIDCD NIH HHS K08 DC006211-05 / NIDCD NIH HHS R01DC02971 / NIDCD NIH HHS
Language: English
Date published: 12/2010
Academic Unit: Molecular Physiology and Biophysics; Chemical and Biochemical Engineering; Neurosurgery; Otolaryngology
Record Identifier: 9984007172402771

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