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CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3

BACKGROUND: Lung cancer is the most commonly diagnosed cancer and leading cause of cancer death, with 80%–85% of non‐small cell lung cancer (NSCLC). Circular RNAs (circRNAs) have been shown to be promising early diagnostic and therapeutic molecular biomarkers for NSCLC. However, biological role and...

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Autores principales: Shi, Fengfeng, Yang, Qin, Shen, Dongdong, Chen, Jianwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373355/
https://www.ncbi.nlm.nih.gov/pubmed/34313353
http://dx.doi.org/10.1002/jcla.23865
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author Shi, Fengfeng
Yang, Qin
Shen, Dongdong
Chen, Jianwei
author_facet Shi, Fengfeng
Yang, Qin
Shen, Dongdong
Chen, Jianwei
author_sort Shi, Fengfeng
collection PubMed
description BACKGROUND: Lung cancer is the most commonly diagnosed cancer and leading cause of cancer death, with 80%–85% of non‐small cell lung cancer (NSCLC). Circular RNAs (circRNAs) have been shown to be promising early diagnostic and therapeutic molecular biomarkers for NSCLC. However, biological role and regulatory mechanism of circRNA WHSC1 (circWHSC1) in NSCLC are unknown. Therefore, we aim to explore the function and mechanism of circWHSC1 in NSCLC oncogenesis and progression. METHODS: qRT‐PCR was used for circWHSC1 level evaluation; Kaplan‐Meier was used for survival analysis; bioinformatics, dual‐luciferase activity, and RNA pull‐down were used for evaluating competing endogenous RNA (ceRNA) network; cell viability, colony formation, apoptosis, migration, and invasion were used for cell function analysis; function gain and loss with rescue experiments were used for exploring mechanism of circWHSC1 in NSCLC development. RESULTS: Significantly up‐regulated circWHSC1 and down‐regulated microRNA‐296‐3p (miR‐296‐3p) were identified in NSCLC tissues and cells. Up‐regulated circWHSC1 was associated with poor prognosis in NSCLC patients. MiR‐296‐3p was sponged by circWHSC1, and AKT serine/threonine kinase 3 (AKT3) was target of miR‐296‐3p; meanwhile, miR‐296‐3p over‐expression significantly down‐regulated AKT3 expression, and co‐transfecting anti‐miR‐296‐3p rescued circWHSC1 silence caused AKT3 down‐regulation. CircWHSC1 silence significantly inhibited colony formation, viability, invasion, and migration, while increased NSCLC cell apoptosis, which were partially rescued by anti‐miR‐296‐3p. CONCLUSION: CircWHSC1 is an independent indicator of poor prognosis in NSCLC patients, and functions as a ceRNA of miR‐296‐3p to up‐regulate AKT3, consequently promotes NSCLC cell growth and metastasis. Targeting circWHSC1 might be a prospective strategy for diagnosis, therapeutics, and prognosis of NSCLC.
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spelling pubmed-83733552021-08-24 CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3 Shi, Fengfeng Yang, Qin Shen, Dongdong Chen, Jianwei J Clin Lab Anal Research Articles BACKGROUND: Lung cancer is the most commonly diagnosed cancer and leading cause of cancer death, with 80%–85% of non‐small cell lung cancer (NSCLC). Circular RNAs (circRNAs) have been shown to be promising early diagnostic and therapeutic molecular biomarkers for NSCLC. However, biological role and regulatory mechanism of circRNA WHSC1 (circWHSC1) in NSCLC are unknown. Therefore, we aim to explore the function and mechanism of circWHSC1 in NSCLC oncogenesis and progression. METHODS: qRT‐PCR was used for circWHSC1 level evaluation; Kaplan‐Meier was used for survival analysis; bioinformatics, dual‐luciferase activity, and RNA pull‐down were used for evaluating competing endogenous RNA (ceRNA) network; cell viability, colony formation, apoptosis, migration, and invasion were used for cell function analysis; function gain and loss with rescue experiments were used for exploring mechanism of circWHSC1 in NSCLC development. RESULTS: Significantly up‐regulated circWHSC1 and down‐regulated microRNA‐296‐3p (miR‐296‐3p) were identified in NSCLC tissues and cells. Up‐regulated circWHSC1 was associated with poor prognosis in NSCLC patients. MiR‐296‐3p was sponged by circWHSC1, and AKT serine/threonine kinase 3 (AKT3) was target of miR‐296‐3p; meanwhile, miR‐296‐3p over‐expression significantly down‐regulated AKT3 expression, and co‐transfecting anti‐miR‐296‐3p rescued circWHSC1 silence caused AKT3 down‐regulation. CircWHSC1 silence significantly inhibited colony formation, viability, invasion, and migration, while increased NSCLC cell apoptosis, which were partially rescued by anti‐miR‐296‐3p. CONCLUSION: CircWHSC1 is an independent indicator of poor prognosis in NSCLC patients, and functions as a ceRNA of miR‐296‐3p to up‐regulate AKT3, consequently promotes NSCLC cell growth and metastasis. Targeting circWHSC1 might be a prospective strategy for diagnosis, therapeutics, and prognosis of NSCLC. John Wiley and Sons Inc. 2021-07-27 /pmc/articles/PMC8373355/ /pubmed/34313353 http://dx.doi.org/10.1002/jcla.23865 Text en © 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Shi, Fengfeng
Yang, Qin
Shen, Dongdong
Chen, Jianwei
CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3
title CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3
title_full CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3
title_fullStr CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3
title_full_unstemmed CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3
title_short CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3
title_sort circrna whsc1 promotes non‐small cell lung cancer progression via sponging microrna‐296‐3p and up‐regulating expression of akt serine/threonine kinase 3
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373355/
https://www.ncbi.nlm.nih.gov/pubmed/34313353
http://dx.doi.org/10.1002/jcla.23865
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