Cargando…
Circular RNA Protein Tyrosine Kinase 2 Promotes Cell Proliferation, Migration and Suppresses Apoptosis via Activating MicroRNA-638 Mediated MEK/ERK, WNT/β-Catenin Signaling Pathways in Multiple Myeloma
Our previous study observed that circular RNA protein tyrosine kinase 2 (circ-PTK2) was upregulated and correlated with worse clinical features and unfavorable prognosis in multiple myeloma (MM) patients. Thus, this study aimed to further characterize the regulatory function of circ-PTK2 on cell mal...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355695/ https://www.ncbi.nlm.nih.gov/pubmed/34395238 http://dx.doi.org/10.3389/fonc.2021.648189 |
_version_ | 1783736811787386880 |
---|---|
author | Zhou, Fan Wang, Dongjiao Zhou, Nian Chen, Haimin Shi, Haotian Peng, Rong Wei, Wei Wu, Lixia |
author_facet | Zhou, Fan Wang, Dongjiao Zhou, Nian Chen, Haimin Shi, Haotian Peng, Rong Wei, Wei Wu, Lixia |
author_sort | Zhou, Fan |
collection | PubMed |
description | Our previous study observed that circular RNA protein tyrosine kinase 2 (circ-PTK2) was upregulated and correlated with worse clinical features and unfavorable prognosis in multiple myeloma (MM) patients. Thus, this study aimed to further characterize the regulatory function of circ-PTK2 on cell malignant activities and its target microRNA-638 (miR-638) as well as downstream MEK/ERK, WNT/β-catenin signaling pathways in MM. The effect of circ-PTK2 on MM cell proliferation, apoptosis, migration, invasion and its potential target miRNAs was assessed by transfecting circ-PTK2 overexpression plasmids into U226 cells and circ-PTK2 knock-down plasmids into LP-1 cells. Furthermore, the interaction between circ-PTK2 and miR-638 mediated MEK/ERK and WNT/β-catenin signaling pathways was validated by rescue experiments. Circ-PTK2 was overexpressed in most MM cell lines compared to normal plasma cells. Overexpressing circ-PTK2 promoted proliferation and migration, inhibited apoptosis in U266 cells, but did not affect cell invasion; knocking down circ-PTK2 achieved opposite effect in LP-1 cells. Besides, circ-PTK2 reversely regulated miR-638 expression but not miR-4690, miR-6724, miR-6749 or miR-6775. The following luciferase reporter assay illustrated the direct bind of circ-PTK2 towards miR-638. In rescue experiments, overexpressing miR-638 suppressed proliferation, migration, while promoted apoptosis in both wild U266 cells and circ-PTK2-overexpressed U266 cells; meanwhile, overexpressing miR-638 also suppressed MEK/ERK and WNT/β-catenin pathways in both wild U266 cells and circ-PTK2-overexpressed U266 cells. Knocking down miR-638 achieved opposite effect in both wild LP-1 cells and circ-PTK2-knocked-down LP-1 cells. In conclusion, circ-PTK2 promotes cell proliferation, migration, suppresses cell apoptosis via miR-638 mediated MEK&ERK and WNT&β-catenin signaling pathways in MM. |
format | Online Article Text |
id | pubmed-8355695 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83556952021-08-12 Circular RNA Protein Tyrosine Kinase 2 Promotes Cell Proliferation, Migration and Suppresses Apoptosis via Activating MicroRNA-638 Mediated MEK/ERK, WNT/β-Catenin Signaling Pathways in Multiple Myeloma Zhou, Fan Wang, Dongjiao Zhou, Nian Chen, Haimin Shi, Haotian Peng, Rong Wei, Wei Wu, Lixia Front Oncol Oncology Our previous study observed that circular RNA protein tyrosine kinase 2 (circ-PTK2) was upregulated and correlated with worse clinical features and unfavorable prognosis in multiple myeloma (MM) patients. Thus, this study aimed to further characterize the regulatory function of circ-PTK2 on cell malignant activities and its target microRNA-638 (miR-638) as well as downstream MEK/ERK, WNT/β-catenin signaling pathways in MM. The effect of circ-PTK2 on MM cell proliferation, apoptosis, migration, invasion and its potential target miRNAs was assessed by transfecting circ-PTK2 overexpression plasmids into U226 cells and circ-PTK2 knock-down plasmids into LP-1 cells. Furthermore, the interaction between circ-PTK2 and miR-638 mediated MEK/ERK and WNT/β-catenin signaling pathways was validated by rescue experiments. Circ-PTK2 was overexpressed in most MM cell lines compared to normal plasma cells. Overexpressing circ-PTK2 promoted proliferation and migration, inhibited apoptosis in U266 cells, but did not affect cell invasion; knocking down circ-PTK2 achieved opposite effect in LP-1 cells. Besides, circ-PTK2 reversely regulated miR-638 expression but not miR-4690, miR-6724, miR-6749 or miR-6775. The following luciferase reporter assay illustrated the direct bind of circ-PTK2 towards miR-638. In rescue experiments, overexpressing miR-638 suppressed proliferation, migration, while promoted apoptosis in both wild U266 cells and circ-PTK2-overexpressed U266 cells; meanwhile, overexpressing miR-638 also suppressed MEK/ERK and WNT/β-catenin pathways in both wild U266 cells and circ-PTK2-overexpressed U266 cells. Knocking down miR-638 achieved opposite effect in both wild LP-1 cells and circ-PTK2-knocked-down LP-1 cells. In conclusion, circ-PTK2 promotes cell proliferation, migration, suppresses cell apoptosis via miR-638 mediated MEK&ERK and WNT&β-catenin signaling pathways in MM. Frontiers Media S.A. 2021-07-28 /pmc/articles/PMC8355695/ /pubmed/34395238 http://dx.doi.org/10.3389/fonc.2021.648189 Text en Copyright © 2021 Zhou, Wang, Zhou, Chen, Shi, Peng, Wei and Wu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Zhou, Fan Wang, Dongjiao Zhou, Nian Chen, Haimin Shi, Haotian Peng, Rong Wei, Wei Wu, Lixia Circular RNA Protein Tyrosine Kinase 2 Promotes Cell Proliferation, Migration and Suppresses Apoptosis via Activating MicroRNA-638 Mediated MEK/ERK, WNT/β-Catenin Signaling Pathways in Multiple Myeloma |
title | Circular RNA Protein Tyrosine Kinase 2 Promotes Cell Proliferation, Migration and Suppresses Apoptosis via Activating MicroRNA-638 Mediated MEK/ERK, WNT/β-Catenin Signaling Pathways in Multiple Myeloma |
title_full | Circular RNA Protein Tyrosine Kinase 2 Promotes Cell Proliferation, Migration and Suppresses Apoptosis via Activating MicroRNA-638 Mediated MEK/ERK, WNT/β-Catenin Signaling Pathways in Multiple Myeloma |
title_fullStr | Circular RNA Protein Tyrosine Kinase 2 Promotes Cell Proliferation, Migration and Suppresses Apoptosis via Activating MicroRNA-638 Mediated MEK/ERK, WNT/β-Catenin Signaling Pathways in Multiple Myeloma |
title_full_unstemmed | Circular RNA Protein Tyrosine Kinase 2 Promotes Cell Proliferation, Migration and Suppresses Apoptosis via Activating MicroRNA-638 Mediated MEK/ERK, WNT/β-Catenin Signaling Pathways in Multiple Myeloma |
title_short | Circular RNA Protein Tyrosine Kinase 2 Promotes Cell Proliferation, Migration and Suppresses Apoptosis via Activating MicroRNA-638 Mediated MEK/ERK, WNT/β-Catenin Signaling Pathways in Multiple Myeloma |
title_sort | circular rna protein tyrosine kinase 2 promotes cell proliferation, migration and suppresses apoptosis via activating microrna-638 mediated mek/erk, wnt/β-catenin signaling pathways in multiple myeloma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355695/ https://www.ncbi.nlm.nih.gov/pubmed/34395238 http://dx.doi.org/10.3389/fonc.2021.648189 |
work_keys_str_mv | AT zhoufan circularrnaproteintyrosinekinase2promotescellproliferationmigrationandsuppressesapoptosisviaactivatingmicrorna638mediatedmekerkwntbcateninsignalingpathwaysinmultiplemyeloma AT wangdongjiao circularrnaproteintyrosinekinase2promotescellproliferationmigrationandsuppressesapoptosisviaactivatingmicrorna638mediatedmekerkwntbcateninsignalingpathwaysinmultiplemyeloma AT zhounian circularrnaproteintyrosinekinase2promotescellproliferationmigrationandsuppressesapoptosisviaactivatingmicrorna638mediatedmekerkwntbcateninsignalingpathwaysinmultiplemyeloma AT chenhaimin circularrnaproteintyrosinekinase2promotescellproliferationmigrationandsuppressesapoptosisviaactivatingmicrorna638mediatedmekerkwntbcateninsignalingpathwaysinmultiplemyeloma AT shihaotian circularrnaproteintyrosinekinase2promotescellproliferationmigrationandsuppressesapoptosisviaactivatingmicrorna638mediatedmekerkwntbcateninsignalingpathwaysinmultiplemyeloma AT pengrong circularrnaproteintyrosinekinase2promotescellproliferationmigrationandsuppressesapoptosisviaactivatingmicrorna638mediatedmekerkwntbcateninsignalingpathwaysinmultiplemyeloma AT weiwei circularrnaproteintyrosinekinase2promotescellproliferationmigrationandsuppressesapoptosisviaactivatingmicrorna638mediatedmekerkwntbcateninsignalingpathwaysinmultiplemyeloma AT wulixia circularrnaproteintyrosinekinase2promotescellproliferationmigrationandsuppressesapoptosisviaactivatingmicrorna638mediatedmekerkwntbcateninsignalingpathwaysinmultiplemyeloma |