A SNP of miR-146a is involved in bladder cancer relapse by affecting the function of bladder cancer stem cells via the miR-146a signallings
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd..
MiR-146a-5p in urine samples was recently reported to be possibly used as a prognostic marker for bladder cancer (BC). Interestingly, YAP1 and COX2 were both demonstrated to function as stem cell regulators in BC. Therefore, in this study, we aimed to establish the molecular mechanism underlying the role of miR-146a, YAP1 and COX2 in BC relapse. We also studied the possibility of using the C > G genotype of miR-146a rs2910164 SNP as an indicator of BC relapse. A total of 170 BC patients were assigned into different groups based on their genotypes of rs2910164 SNP. Kaplan-Meier survival curves were plotted to compare the recurrence-free rate among these groups. Real-time PCR, Western Blot, bioinformatic analysis, luciferase assay and IHC assay were conducted to study the role of rs2910164 SNP in the progression of BC. Accordingly, GC/CC-genotyped patients presented a higher risk of recurrence when compared with GG-genotyped patients, while the expression of BC regulators was influenced by the presence of rs2910164. COX2 mRNA and YAP1 mRNA were, respectively, validated as direct target genes of miR-146a, and the expression of YAP1 and COX2 mRNA/protein was both suppressed by miR-146a precursors. The expression of ALDH1A1 mRNA/protein was inhibited upon the down-regulation of YAP1, while the expression of let7 and SOX2 mRNA/protein was inhibited upon the down-regulation of COX2. In conclusion, two signalling pathways, miR-146a/YAP1/ALDH1A1 and miR-146a/COX2/PGE2/let7/SOX2, were modulated by miR-146a. As an SNP regulating the expression of miR-146a, the rs2910164 G > C SNP could be utilized as a biomarker for BC relapse.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
Journal of cellular and molecular medicine - 24(2020), 15 vom: 01. Aug., Seite 8545-8556 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Tianen [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 13.05.2021 Date Revised 04.12.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/jcmm.15480 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM311750664 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM311750664 | ||
| 003 | DE-627 | ||
| 005 | 20231225142927.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/jcmm.15480 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1039.xml |
| 035 | |a (DE-627)NLM311750664 | ||
| 035 | |a (NLM)32596945 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Tianen |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A SNP of miR-146a is involved in bladder cancer relapse by affecting the function of bladder cancer stem cells via the miR-146a signallings |
| 264 | 1 | |c 2020 | |
| 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 13.05.2021 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. | ||
| 520 | |a MiR-146a-5p in urine samples was recently reported to be possibly used as a prognostic marker for bladder cancer (BC). Interestingly, YAP1 and COX2 were both demonstrated to function as stem cell regulators in BC. Therefore, in this study, we aimed to establish the molecular mechanism underlying the role of miR-146a, YAP1 and COX2 in BC relapse. We also studied the possibility of using the C > G genotype of miR-146a rs2910164 SNP as an indicator of BC relapse. A total of 170 BC patients were assigned into different groups based on their genotypes of rs2910164 SNP. Kaplan-Meier survival curves were plotted to compare the recurrence-free rate among these groups. Real-time PCR, Western Blot, bioinformatic analysis, luciferase assay and IHC assay were conducted to study the role of rs2910164 SNP in the progression of BC. Accordingly, GC/CC-genotyped patients presented a higher risk of recurrence when compared with GG-genotyped patients, while the expression of BC regulators was influenced by the presence of rs2910164. COX2 mRNA and YAP1 mRNA were, respectively, validated as direct target genes of miR-146a, and the expression of YAP1 and COX2 mRNA/protein was both suppressed by miR-146a precursors. The expression of ALDH1A1 mRNA/protein was inhibited upon the down-regulation of YAP1, while the expression of let7 and SOX2 mRNA/protein was inhibited upon the down-regulation of COX2. In conclusion, two signalling pathways, miR-146a/YAP1/ALDH1A1 and miR-146a/COX2/PGE2/let7/SOX2, were modulated by miR-146a. As an SNP regulating the expression of miR-146a, the rs2910164 G > C SNP could be utilized as a biomarker for BC relapse | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BC stem cell | |
| 650 | 4 | |a bladder cancer | |
| 650 | 4 | |a miR-146a | |
| 650 | 4 | |a relapse | |
| 650 | 4 | |a rs2910164 | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a MIRN146 microRNA, human |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a YAP-Signaling Proteins |2 NLM | |
| 650 | 7 | |a YAP1 protein, human |2 NLM | |
| 650 | 7 | |a Cyclooxygenase 2 |2 NLM | |
| 650 | 7 | |a EC 1.14.99.1 |2 NLM | |
| 700 | 1 | |a Yang, Yanfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhiyong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xuechong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Dongsheng |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Jinxing |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of cellular and molecular medicine |d 2000 |g 24(2020), 15 vom: 01. Aug., Seite 8545-8556 |w (DE-627)NLM118801236 |x 1582-4934 |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2020 |g number:15 |g day:01 |g month:08 |g pages:8545-8556 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/jcmm.15480 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2020 |e 15 |b 01 |c 08 |h 8545-8556 | ||