Cargando…

LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4

BACKGROUND: LncRNA TP73-AS1 has been revealed to exert a noteworthy impact on the occurrence and advancement of different cancers. In this study, we explored the function of TP73-AS1 in tumor growth, cell progression as well as the relevant molecular mechanism in non-small-cell lung cancer (NSCLC)....

Descripción completa

Detalles Bibliográficos
Autores principales: Tong, Yueyang, Feng, Zhemin, Li, Yaqian, Yan, Chenxi, He, Wenbo, Chen, Xueyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481391/
https://www.ncbi.nlm.nih.gov/pubmed/36118078
http://dx.doi.org/10.1155/2022/4098271
_version_ 1784791255960518656
author Tong, Yueyang
Feng, Zhemin
Li, Yaqian
Yan, Chenxi
He, Wenbo
Chen, Xueyuan
author_facet Tong, Yueyang
Feng, Zhemin
Li, Yaqian
Yan, Chenxi
He, Wenbo
Chen, Xueyuan
author_sort Tong, Yueyang
collection PubMed
description BACKGROUND: LncRNA TP73-AS1 has been revealed to exert a noteworthy impact on the occurrence and advancement of different cancers. In this study, we explored the function of TP73-AS1 in tumor growth, cell progression as well as the relevant molecular mechanism in non-small-cell lung cancer (NSCLC). METHODS: QRT-PCR was employed to assess the expression of TP73-AS1, miR‐125a-3p, and actinin alpha 4 (ACTN4) in NSCLC cells. The biological effect of TP73-AS1 on NSCLC cells was assessed by cell transfection, CCK8, and transwell experiments. We further predicted the interaction among RNAs (TP73-AS1, miR-125a-3p, and ACTN4) through bioinformatics online tools and verified via luciferase reporter, RNA immunoprecipitation, and qRT-PCR assays. Xenograft models of SPC-A1 cells were conducted to test how TP73-AS1 regulates tumorigenesis. Western blot, as well as the immunohistochemistry (IHC) assays, was utilized to measure the expression levels. Functions of TP73-AS1 in NSCLC progression through the miR-125a-3p/ACTN4 axis were investigated by rescue experiments. RESULTS: Knockdown of TP73-AS1 suppressed the growth and simultaneously attenuated the migration and invasion ability of NSCLC SPC-A1 and A549 cells. Bioinformatics and molecular mechanism assays demonstrated that TP73-AS1 could bind to miR-125a-3p/ACTN4 and regulate their expression. Moreover, the rescued‐function experiment demonstrated that suppressing miR-125a-3p or elevating ACTN4 turned around the suppression effect of sh-TP73-AS1 on NSCLC progression. TP73-AS1 inhibition could also inhibit the NSCLC tumor growth and correspondingly regulated the expression of miR-125a-3p and ACTN4 in the tumor xenograft model. CONCLUSION: The present study indicated that TP73-AS1 affects NSCLC progression through a new competitive RNA (ceRNA) regulatory network of miR-125a-3p/ACTN4, providing an underlying target for NSCLC treatment in the future.
format Online
Article
Text
id pubmed-9481391
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-94813912022-09-17 LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4 Tong, Yueyang Feng, Zhemin Li, Yaqian Yan, Chenxi He, Wenbo Chen, Xueyuan Evid Based Complement Alternat Med Research Article BACKGROUND: LncRNA TP73-AS1 has been revealed to exert a noteworthy impact on the occurrence and advancement of different cancers. In this study, we explored the function of TP73-AS1 in tumor growth, cell progression as well as the relevant molecular mechanism in non-small-cell lung cancer (NSCLC). METHODS: QRT-PCR was employed to assess the expression of TP73-AS1, miR‐125a-3p, and actinin alpha 4 (ACTN4) in NSCLC cells. The biological effect of TP73-AS1 on NSCLC cells was assessed by cell transfection, CCK8, and transwell experiments. We further predicted the interaction among RNAs (TP73-AS1, miR-125a-3p, and ACTN4) through bioinformatics online tools and verified via luciferase reporter, RNA immunoprecipitation, and qRT-PCR assays. Xenograft models of SPC-A1 cells were conducted to test how TP73-AS1 regulates tumorigenesis. Western blot, as well as the immunohistochemistry (IHC) assays, was utilized to measure the expression levels. Functions of TP73-AS1 in NSCLC progression through the miR-125a-3p/ACTN4 axis were investigated by rescue experiments. RESULTS: Knockdown of TP73-AS1 suppressed the growth and simultaneously attenuated the migration and invasion ability of NSCLC SPC-A1 and A549 cells. Bioinformatics and molecular mechanism assays demonstrated that TP73-AS1 could bind to miR-125a-3p/ACTN4 and regulate their expression. Moreover, the rescued‐function experiment demonstrated that suppressing miR-125a-3p or elevating ACTN4 turned around the suppression effect of sh-TP73-AS1 on NSCLC progression. TP73-AS1 inhibition could also inhibit the NSCLC tumor growth and correspondingly regulated the expression of miR-125a-3p and ACTN4 in the tumor xenograft model. CONCLUSION: The present study indicated that TP73-AS1 affects NSCLC progression through a new competitive RNA (ceRNA) regulatory network of miR-125a-3p/ACTN4, providing an underlying target for NSCLC treatment in the future. Hindawi 2022-09-09 /pmc/articles/PMC9481391/ /pubmed/36118078 http://dx.doi.org/10.1155/2022/4098271 Text en Copyright © 2022 Yueyang Tong et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Tong, Yueyang
Feng, Zhemin
Li, Yaqian
Yan, Chenxi
He, Wenbo
Chen, Xueyuan
LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4
title LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4
title_full LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4
title_fullStr LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4
title_full_unstemmed LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4
title_short LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4
title_sort lncrna tp73-as1 exacerbates the non-small-cell lung cancer (nsclc) process via regulating mir-125a-3p-mediated actn4
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481391/
https://www.ncbi.nlm.nih.gov/pubmed/36118078
http://dx.doi.org/10.1155/2022/4098271
work_keys_str_mv AT tongyueyang lncrnatp73as1exacerbatesthenonsmallcelllungcancernsclcprocessviaregulatingmir125a3pmediatedactn4
AT fengzhemin lncrnatp73as1exacerbatesthenonsmallcelllungcancernsclcprocessviaregulatingmir125a3pmediatedactn4
AT liyaqian lncrnatp73as1exacerbatesthenonsmallcelllungcancernsclcprocessviaregulatingmir125a3pmediatedactn4
AT yanchenxi lncrnatp73as1exacerbatesthenonsmallcelllungcancernsclcprocessviaregulatingmir125a3pmediatedactn4
AT hewenbo lncrnatp73as1exacerbatesthenonsmallcelllungcancernsclcprocessviaregulatingmir125a3pmediatedactn4
AT chenxueyuan lncrnatp73as1exacerbatesthenonsmallcelllungcancernsclcprocessviaregulatingmir125a3pmediatedactn4