MiR-338-5p sensitizes glioblastoma cells to radiation through
regulation of genes involved in DNA damage response

J 2016

MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response

BEŠŠE, Andrej, Jiří ŠÁNA, Radek LAKOMÝ, Leoš KŘEN, Pavel FADRUS et. al.

Basic information

Original name

MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response

Authors

BEŠŠE, Andrej (703 Slovakia, belonging to the institution), Jiří ŠÁNA (203 Czech Republic, belonging to the institution), Radek LAKOMÝ (203 Czech Republic, belonging to the institution), Leoš KŘEN (203 Czech Republic, belonging to the institution), Pavel FADRUS (203 Czech Republic, belonging to the institution), Martin SMRČKA (203 Czech Republic, belonging to the institution), Markéta HERMANOVÁ (203 Czech Republic, belonging to the institution), Radim JANČÁLEK (203 Czech Republic, belonging to the institution), Stefan REGULI (203 Czech Republic), Radim LIPINA (203 Czech Republic), Marek SVOBODA (203 Czech Republic, belonging to the institution), Pavel ŠLAMPA (203 Czech Republic) and Ondřej SLABÝ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Tumor Biology, Dordrecht, Springer, 2016, 1010-4283

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.650

RIV identification code

RIV/00216224:14740/16:00088839

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1007/s13277-015-4654-x

UT WoS

000376464700071

Keywords (in Czech)

Multiformní glioblastom; radiace; resistence; miRNA; miR-338-5p

Keywords in English

Glioblastoma multiforme; GBM; Radiation resistance; miRNA; miRNA338-5p

Abstract

V originále

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with an extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to the treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain-specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and miR-338-5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased cell proliferation, increased cell cycle arrest, and apoptosis in comparison to irradiation-only cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, and ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation, and cell cycle regulation. To our knowledge, this is the first study to describe the role of miR-338-5p in GBM and its potential to improve the sensitivity of GBM to radiation.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

NT13514, research and development project

Name: Analýza mikroRNA v glioblastomových kmenových buňkách: predikce léčebné odpovědi a identifikace nových terapeutických cílů u pacientů s glioblastomem

Files attached

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Request the author's version of the file

Citovat

BEŠŠE, Andrej, Jiří ŠÁNA, Radek LAKOMÝ, Leoš KŘEN, Pavel FADRUS, Martin SMRČKA, Markéta HERMANOVÁ, Radim JANČÁLEK, Stefan REGULI, Radim LIPINA, Marek SVOBODA, Pavel ŠLAMPA and Ondřej SLABÝ. MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response. Tumor Biology. Dordrecht: Springer, 2016, vol. 37, No 6, p. 7719-7727. ISSN 1010-4283. Available from: https://dx.doi.org/10.1007/s13277-015-4654-x.

@article{1323482,
   author = {Bešše, Andrej and Šána, Jiří and Lakomý, Radek and Křen, Leoš and Fadrus, Pavel and Smrčka, Martin and Hermanová, Markéta and Jančálek, Radim and Reguli, Stefan and Lipina, Radim and Svoboda, Marek and Šlampa, Pavel and Slabý, Ondřej},
   article_location = {Dordrecht},
   article_number = {6},
   doi = {http://dx.doi.org/10.1007/s13277-015-4654-x},
   keywords = {Glioblastoma multiforme; GBM; Radiation resistance; miRNA; miRNA338-5p},
   language = {eng},
   issn = {1010-4283},
   journal = {Tumor Biology},
   title = {MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response},
   url = {http://link.springer.com/article/10.1007%2Fs13277-015-4654-x},
   volume = {37},
   year = {2016}
}

TY  - JOUR
ID  - 1323482
AU  - Bešše, Andrej - Šána, Jiří - Lakomý, Radek - Křen, Leoš - Fadrus, Pavel - Smrčka, Martin - Hermanová, Markéta - Jančálek, Radim - Reguli, Stefan - Lipina, Radim - Svoboda, Marek - Šlampa, Pavel - Slabý, Ondřej
PY  - 2016
TI  - MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response
JF  - Tumor Biology
VL  - 37
IS  - 6
SP  - 7719-7727
EP  - 7719-7727
PB  - Springer
SN  - 10104283
KW  - Glioblastoma multiforme
KW  - GBM
KW  - Radiation resistance
KW  - miRNA
KW  - miRNA338-5p
UR  - http://link.springer.com/article/10.1007%2Fs13277-015-4654-x
L2  - http://link.springer.com/article/10.1007%2Fs13277-015-4654-x
N2  - Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with an extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to the treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain-specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and miR-338-5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased cell proliferation, increased cell cycle arrest, and apoptosis in comparison to irradiation-only cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, and ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation, and cell cycle regulation. To our knowledge, this is the first study to describe the role of miR-338-5p in GBM and its potential to improve the sensitivity of GBM to radiation.
ER  -

BEŠŠE, Andrej, Jiří ŠÁNA, Radek LAKOMÝ, Leoš KŘEN, Pavel FADRUS, Martin SMRČKA, Markéta HERMANOVÁ, Radim JANČÁLEK, Stefan REGULI, Radim LIPINA, Marek SVOBODA, Pavel ŠLAMPA and Ondřej SLABÝ. MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response. \textit{Tumor Biology}. Dordrecht: Springer, 2016, vol.~37, No~6, p.~7719-7727. ISSN~1010-4283. Available from: https://dx.doi.org/10.1007/s13277-015-4654-x.

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