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Overexpression of miR‑361‑5p plays an oncogenic role in human lung adenocarcinoma through the regulation of SMAD2

The silencing of Bcl-xL in the non-small cell lung cancer (NSCLC) cell line, A549, downregulates miR-361-5p expression. This study aimed to determine the biological effects of miR-361-5p on NSCLC, and to elucidate the molecular mechanisms through which apoptosis is regulated. MicroRNA (miRNA or miR)...

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Main Authors: Othman, Norahayu, Nagoor, Noor Hasima
Format: Article
Published: Spandidos Publications 2018
Subjects:
Q Science (General)
QH Natural history
Online Access:http://eprints.um.edu.my/19941/
https://doi.org/10.3892/ijo.2018.4602
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spelling my.um.eprints.199412019-01-11T01:24:51Z http://eprints.um.edu.my/19941/ Overexpression of miR‑361‑5p plays an oncogenic role in human lung adenocarcinoma through the regulation of SMAD2 Othman, Norahayu Nagoor, Noor Hasima Q Science (General) QH Natural history The silencing of Bcl-xL in the non-small cell lung cancer (NSCLC) cell line, A549, downregulates miR-361-5p expression. This study aimed to determine the biological effects of miR-361-5p on NSCLC, and to elucidate the molecular mechanisms through which apoptosis is regulated. MicroRNA (miRNA or miR) functional analyses were performed via transfection of miR-361-5p mimics and inhibitors, demonstrating that the inhibition of miR-361-5p induced the apoptosis of NSCLC cells. To elucidate the function of miR-361-5p in vivo, cells transfected with miR-361-5p inhibitors were microinjected into zebrafish embryos, and immunostained using antibodies to detect the active form of caspase-3. Co-transfection with siBcl-xL and miR-361-5p mimics illustrated the association between Bcl-xL, miR-361-5p and apoptosis; miR-361-5p mimics blocked the apoptosis initiated by siBcl-xL. Luciferase reporter assays identified mothers against decapentaplegic homolog 2 (SMAD2) as a novel target of miR-361-5p and the reduction of its protein level was validated by western blot analysis. To confirm the molecular mechanisms through which apoptosis is regulated, gene rescue experiments revealed that the ectopic expression of SMAD2 attenuated the inhibitory effects on apoptosis induced by miR-361-5p. In this study, to the best of our knowledge, we provide the first evidence that miR-361-5p functions as an oncomiR in A549 and SK-LU-1 cells through the regulation of SMAD2, suggesting that miR-361-5p may be employed as a potential therapeutic target for the miRNA-based therapy of NSCLC. Spandidos Publications 2018 Article PeerReviewed Othman, Norahayu and Nagoor, Noor Hasima (2018) Overexpression of miR‑361‑5p plays an oncogenic role in human lung adenocarcinoma through the regulation of SMAD2. International Journal of Oncology, 54 (1). pp. 306-314. ISSN 1019-6439 https://doi.org/10.3892/ijo.2018.4602 doi:10.3892/ijo.2018.4602
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic Q Science (General)
QH Natural history
spellingShingle Q Science (General)
QH Natural history
Othman, Norahayu
Nagoor, Noor Hasima
Overexpression of miR‑361‑5p plays an oncogenic role in human lung adenocarcinoma through the regulation of SMAD2
description The silencing of Bcl-xL in the non-small cell lung cancer (NSCLC) cell line, A549, downregulates miR-361-5p expression. This study aimed to determine the biological effects of miR-361-5p on NSCLC, and to elucidate the molecular mechanisms through which apoptosis is regulated. MicroRNA (miRNA or miR) functional analyses were performed via transfection of miR-361-5p mimics and inhibitors, demonstrating that the inhibition of miR-361-5p induced the apoptosis of NSCLC cells. To elucidate the function of miR-361-5p in vivo, cells transfected with miR-361-5p inhibitors were microinjected into zebrafish embryos, and immunostained using antibodies to detect the active form of caspase-3. Co-transfection with siBcl-xL and miR-361-5p mimics illustrated the association between Bcl-xL, miR-361-5p and apoptosis; miR-361-5p mimics blocked the apoptosis initiated by siBcl-xL. Luciferase reporter assays identified mothers against decapentaplegic homolog 2 (SMAD2) as a novel target of miR-361-5p and the reduction of its protein level was validated by western blot analysis. To confirm the molecular mechanisms through which apoptosis is regulated, gene rescue experiments revealed that the ectopic expression of SMAD2 attenuated the inhibitory effects on apoptosis induced by miR-361-5p. In this study, to the best of our knowledge, we provide the first evidence that miR-361-5p functions as an oncomiR in A549 and SK-LU-1 cells through the regulation of SMAD2, suggesting that miR-361-5p may be employed as a potential therapeutic target for the miRNA-based therapy of NSCLC.
format Article
author Othman, Norahayu
Nagoor, Noor Hasima
author_facet Othman, Norahayu
Nagoor, Noor Hasima
author_sort Othman, Norahayu
title Overexpression of miR‑361‑5p plays an oncogenic role in human lung adenocarcinoma through the regulation of SMAD2
title_short Overexpression of miR‑361‑5p plays an oncogenic role in human lung adenocarcinoma through the regulation of SMAD2
title_full Overexpression of miR‑361‑5p plays an oncogenic role in human lung adenocarcinoma through the regulation of SMAD2
title_fullStr Overexpression of miR‑361‑5p plays an oncogenic role in human lung adenocarcinoma through the regulation of SMAD2
title_full_unstemmed Overexpression of miR‑361‑5p plays an oncogenic role in human lung adenocarcinoma through the regulation of SMAD2
title_sort overexpression of mir‑361‑5p plays an oncogenic role in human lung adenocarcinoma through the regulation of smad2
publisher Spandidos Publications
publishDate 2018
url http://eprints.um.edu.my/19941/
https://doi.org/10.3892/ijo.2018.4602
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score 13.211869

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