Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis.

PURPOSE:Oct4 was reported to be one of the most important pluripotency transcription factors in the biology of stem cells including cancer stem cells, and progressed malignant cells. Here we report the investigation of gene expression control of Oct4 by selected human microRNAs and the physiological...

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Main Authors: Axel R Göhring, Stefanie Reuter, Joachim H Clement, Xinlai Cheng, Jannick Theobald, Stefan Wölfl, Ralf Mrowka
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5398498?pdf=render
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author Axel R Göhring
Stefanie Reuter
Joachim H Clement
Xinlai Cheng
Jannick Theobald
Stefan Wölfl
Ralf Mrowka
author_facet Axel R Göhring
Stefanie Reuter
Joachim H Clement
Xinlai Cheng
Jannick Theobald
Stefan Wölfl
Ralf Mrowka
author_sort Axel R Göhring
collection DOAJ
description PURPOSE:Oct4 was reported to be one of the most important pluripotency transcription factors in the biology of stem cells including cancer stem cells, and progressed malignant cells. Here we report the investigation of gene expression control of Oct4 by selected human microRNAs and the physiological effect of Oct4 silencing in invasive cancer cells. METHODS AND RESULTS:High throughput luciferase activity assay revealed the microRNA-299-3p to be the most effective in reducing gene expression of Oct4, which was confirmed by Western blot analysis and Oct4 promoter activity in a target luciferase assay. Furthermore, it could be demonstrated that downregulation of Oct4 by microRNAs-299-3p in breast cancer and fibrosarcoma cells lead to a decreased invasiveness in a microfluidic chip assay. Additionally, microRNA-299-3p causes apoptosis in cancer cells. Comparison with Oct4 specific siRNA transfection confirmed that this effect is primary due to the blockade of Oct4 expression. CONCLUSION:The results suggest that microRNA-299-3p is an interesting target for potential clinical use. It may be able to decrease invasive behaviour of carcinoma cells; or even kill these cells by causing apoptosis.
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spelling doaj.art-feceb3ff4204462db708c4b2ed6c2f0c2022-12-21T17:30:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01124e017491210.1371/journal.pone.0174912Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis.Axel R GöhringStefanie ReuterJoachim H ClementXinlai ChengJannick TheobaldStefan WölflRalf MrowkaPURPOSE:Oct4 was reported to be one of the most important pluripotency transcription factors in the biology of stem cells including cancer stem cells, and progressed malignant cells. Here we report the investigation of gene expression control of Oct4 by selected human microRNAs and the physiological effect of Oct4 silencing in invasive cancer cells. METHODS AND RESULTS:High throughput luciferase activity assay revealed the microRNA-299-3p to be the most effective in reducing gene expression of Oct4, which was confirmed by Western blot analysis and Oct4 promoter activity in a target luciferase assay. Furthermore, it could be demonstrated that downregulation of Oct4 by microRNAs-299-3p in breast cancer and fibrosarcoma cells lead to a decreased invasiveness in a microfluidic chip assay. Additionally, microRNA-299-3p causes apoptosis in cancer cells. Comparison with Oct4 specific siRNA transfection confirmed that this effect is primary due to the blockade of Oct4 expression. CONCLUSION:The results suggest that microRNA-299-3p is an interesting target for potential clinical use. It may be able to decrease invasive behaviour of carcinoma cells; or even kill these cells by causing apoptosis.http://europepmc.org/articles/PMC5398498?pdf=render
spellingShingle Axel R Göhring
Stefanie Reuter
Joachim H Clement
Xinlai Cheng
Jannick Theobald
Stefan Wölfl
Ralf Mrowka
Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis.
PLoS ONE
title Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis.
title_full Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis.
title_fullStr Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis.
title_full_unstemmed Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis.
title_short Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis.
title_sort human microrna 299 3p decreases invasive behavior of cancer cells by downregulation of oct4 expression and causes apoptosis
url http://europepmc.org/articles/PMC5398498?pdf=render
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