Silencing of lncRNA PVT1 by miR-214 inhibits the oncogenic GDF15 signaling and suppresses hepatocarcinogenesis
Copyright © 2019 Elsevier Inc. All rights reserved..
The prognosis for hepatocellular carcinoma (HCC) is dismal. Long noncoding RNA PVT1 has been linked to malignancies and might be a deleterious therapy target. However, the key events controlling its expression in HCC remain undetermined. Here, we address how PVT1 is fine-regulated and its downstream signaling in hepatoma cells. Interestingly, we found that c-Myc and P53 could divergently regulate PVT1 transcription. Oncoprotein c-Myc enhances PVT1 expression, whereas P53 suppresses its expression. We also identified miR-214 as a crucial, negative regulator of PVT1. Consistently, high miR-214 levels were significantly correlated with diminished PVT1 expression in HCC specimens. Silencing of PVT1 by ectopic miR-214 or siRNAs markedly inhibited viability and invasion of HCC cells. In opposition, inhibition of endogenous miR-214 promoted PVT1 expression and enhanced cell proliferation. Notably, oncogenic GDF15 is a potential downstream target of the miR-214-PVT1 signaling. Collectively, our results show that the c-Myc/P53/miR-214-PVT1-GDF15 axis is implicated in HCC development, shedding light on the mechanistic actions of PVT1 and representing potential targets for HCC clinical intervention.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:521 |
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| Enthalten in: |
Biochemical and biophysical research communications - 521(2020), 2 vom: 08. Jan., Seite 478-484 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xiong, Xiangyu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.07.2020 Date Revised 27.07.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2019.10.137 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM302821686 |
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| 100 | 1 | |a Xiong, Xiangyu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Silencing of lncRNA PVT1 by miR-214 inhibits the oncogenic GDF15 signaling and suppresses hepatocarcinogenesis |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Elsevier Inc. All rights reserved. | ||
| 520 | |a The prognosis for hepatocellular carcinoma (HCC) is dismal. Long noncoding RNA PVT1 has been linked to malignancies and might be a deleterious therapy target. However, the key events controlling its expression in HCC remain undetermined. Here, we address how PVT1 is fine-regulated and its downstream signaling in hepatoma cells. Interestingly, we found that c-Myc and P53 could divergently regulate PVT1 transcription. Oncoprotein c-Myc enhances PVT1 expression, whereas P53 suppresses its expression. We also identified miR-214 as a crucial, negative regulator of PVT1. Consistently, high miR-214 levels were significantly correlated with diminished PVT1 expression in HCC specimens. Silencing of PVT1 by ectopic miR-214 or siRNAs markedly inhibited viability and invasion of HCC cells. In opposition, inhibition of endogenous miR-214 promoted PVT1 expression and enhanced cell proliferation. Notably, oncogenic GDF15 is a potential downstream target of the miR-214-PVT1 signaling. Collectively, our results show that the c-Myc/P53/miR-214-PVT1-GDF15 axis is implicated in HCC development, shedding light on the mechanistic actions of PVT1 and representing potential targets for HCC clinical intervention | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a P53 | |
| 650 | 4 | |a PVT1 | |
| 650 | 4 | |a c-Myc | |
| 650 | 4 | |a miR-214 | |
| 650 | 7 | |a GDF15 protein, human |2 NLM | |
| 650 | 7 | |a Growth Differentiation Factor 15 |2 NLM | |
| 650 | 7 | |a MIRN214 microRNA, human |2 NLM | |
| 650 | 7 | |a MYC protein, human |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a PVT1 long-non-coding RNA, human |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-myc |2 NLM | |
| 650 | 7 | |a RNA, Long Noncoding |2 NLM | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 700 | 1 | |a Yuan, Jupeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Nasha |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jibing |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Ming |e verfasserin |4 aut | |
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