Post-transcriptional modulation of protein phosphatase PPP2CA and tumor suppressor PTEN by endogenous siRNA cleaved from hairpin within PTEN mRNA 3'UTR in human liver cells
AIM: Increasing evidence shows that mRNAs exert regulatory function along with coding proteins. Recently we report that a hairpin within YAP mRNA 3'UTR can modulate the Hippo signaling pathway. PTEN is a tumor suppressor, and is mutated in human cancers. In this study we examined whether PTEN mRNA 3'UTR contained a hairpin structure that could regulate gene regulation at the post-transcriptional level.
METHODS: The secondary structure of PTEN mRNA 3'UTR was analyzed using RNAdraw and RNAstructure. Function of hairpin structure derived from the PTEN mRNA 3'UTR was examined using luciferase reporter assay, RT-PCR and Western blotting. RNA-immunoprecipitation (RIP) assay was used to analyze the interaction between PTEN mRNA and microprocessor Drosha and DGCR8. Endogenous siRNA (esiRNA) derived from PTEN mRNA 3'UTR was identified by RT-PCR and rt-PCR, and its target genes were predicted using RNAhybrid.
RESULTS: A bioinformatics analysis revealed that PTEN mRNA contained a hairpin structure (termed PTEN-sh) within 3'UTR, which markedly increased the reporter activities of AP-1 and NF-κB in 293T cells. Moreover, treatment with PTEN-sh (1 and 2 μg) dose-dependently inhibited the expression of PTEN in human liver L-O2 cells. RIP assay demonstrated that the microprocessor Drosha and DGCR8 was bound to PTEN-sh in L-O2 cells, leading to the cleavage of PTEN-sh from PTEN mRNA 3'UTR. In addition, microprocessor Dicer was involved in the processing of PTEN-sh. Interestingly, esiRNA (termed PTEN-sh-3p21) cleaved from PTEN-sh was identified in 293T cells and human liver tissues, which was found to target the mRNA 3'UTRs of protein phosphatase PPP2CA and PTEN in L-O2 cells. Treatment of L-O2 or Chang liver cells with PTEN-sh-3p21 (50, 100 nmol/L) promoted the cell proliferation in dose- and time-dependent manners.
CONCLUSION: The endogenous siRNA (PTEN-sh-3p21) cleaved from PTEN-sh within PTEN mRNA 3'UTR modulates PPP2CA and PTEN at the post-transcriptional level in liver cells.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2016 |
|---|---|
| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
|---|---|
| Enthalten in: |
Acta pharmacologica Sinica - 37(2016), 7 vom: 25. Juli, Seite 898-907 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gao, Yu-En [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 02.08.2017 Date Revised 13.11.2018 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/aps.2016.18 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM259911496 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM259911496 | ||
| 003 | DE-627 | ||
| 005 | 20231224192230.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2016 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/aps.2016.18 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0866.xml |
| 035 | |a (DE-627)NLM259911496 | ||
| 035 | |a (NLM)27133296 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gao, Yu-En |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Post-transcriptional modulation of protein phosphatase PPP2CA and tumor suppressor PTEN by endogenous siRNA cleaved from hairpin within PTEN mRNA 3'UTR in human liver cells |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.08.2017 | ||
| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a AIM: Increasing evidence shows that mRNAs exert regulatory function along with coding proteins. Recently we report that a hairpin within YAP mRNA 3'UTR can modulate the Hippo signaling pathway. PTEN is a tumor suppressor, and is mutated in human cancers. In this study we examined whether PTEN mRNA 3'UTR contained a hairpin structure that could regulate gene regulation at the post-transcriptional level | ||
| 520 | |a METHODS: The secondary structure of PTEN mRNA 3'UTR was analyzed using RNAdraw and RNAstructure. Function of hairpin structure derived from the PTEN mRNA 3'UTR was examined using luciferase reporter assay, RT-PCR and Western blotting. RNA-immunoprecipitation (RIP) assay was used to analyze the interaction between PTEN mRNA and microprocessor Drosha and DGCR8. Endogenous siRNA (esiRNA) derived from PTEN mRNA 3'UTR was identified by RT-PCR and rt-PCR, and its target genes were predicted using RNAhybrid | ||
| 520 | |a RESULTS: A bioinformatics analysis revealed that PTEN mRNA contained a hairpin structure (termed PTEN-sh) within 3'UTR, which markedly increased the reporter activities of AP-1 and NF-κB in 293T cells. Moreover, treatment with PTEN-sh (1 and 2 μg) dose-dependently inhibited the expression of PTEN in human liver L-O2 cells. RIP assay demonstrated that the microprocessor Drosha and DGCR8 was bound to PTEN-sh in L-O2 cells, leading to the cleavage of PTEN-sh from PTEN mRNA 3'UTR. In addition, microprocessor Dicer was involved in the processing of PTEN-sh. Interestingly, esiRNA (termed PTEN-sh-3p21) cleaved from PTEN-sh was identified in 293T cells and human liver tissues, which was found to target the mRNA 3'UTRs of protein phosphatase PPP2CA and PTEN in L-O2 cells. Treatment of L-O2 or Chang liver cells with PTEN-sh-3p21 (50, 100 nmol/L) promoted the cell proliferation in dose- and time-dependent manners | ||
| 520 | |a CONCLUSION: The endogenous siRNA (PTEN-sh-3p21) cleaved from PTEN-sh within PTEN mRNA 3'UTR modulates PPP2CA and PTEN at the post-transcriptional level in liver cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a 3' Untranslated Regions |2 NLM | |
| 650 | 7 | |a DGCR8 protein, human |2 NLM | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a RNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a DICER1 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.1.26.3 |2 NLM | |
| 650 | 7 | |a DROSHA protein, human |2 NLM | |
| 650 | 7 | |a EC 3.1.26.3 |2 NLM | |
| 650 | 7 | |a Ribonuclease III |2 NLM | |
| 650 | 7 | |a EC 3.1.26.3 |2 NLM | |
| 650 | 7 | |a PPP2CA protein, human |2 NLM | |
| 650 | 7 | |a EC 3.1.3.16 |2 NLM | |
| 650 | 7 | |a Protein Phosphatase 2 |2 NLM | |
| 650 | 7 | |a EC 3.1.3.16 |2 NLM | |
| 650 | 7 | |a PTEN Phosphohydrolase |2 NLM | |
| 650 | 7 | |a EC 3.1.3.67 |2 NLM | |
| 650 | 7 | |a PTEN protein, human |2 NLM | |
| 650 | 7 | |a EC 3.1.3.67 |2 NLM | |
| 650 | 7 | |a DEAD-box RNA Helicases |2 NLM | |
| 650 | 7 | |a EC 3.6.4.13 |2 NLM | |
| 700 | 1 | |a Wang, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Fu-Quan |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Jin-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Guang |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Guo-Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Li-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiao-Dong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Acta pharmacologica Sinica |d 2000 |g 37(2016), 7 vom: 25. Juli, Seite 898-907 |w (DE-627)NLM111735181 |x 1745-7254 |7 nnns |
| 773 | 1 | 8 | |g volume:37 |g year:2016 |g number:7 |g day:25 |g month:07 |g pages:898-907 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/aps.2016.18 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 37 |j 2016 |e 7 |b 25 |c 07 |h 898-907 | ||