LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway

Abstract Background Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved. Methods...

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Autores principales:	Yaomei He, Xiulin Jiang, Lincan Duan, Qiuxia Xiong, Yixiao Yuan, Peishen Liu, Liping Jiang, Qiushuo Shen, Song Zhao, Cuiping Yang, Yongbin Chen
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	PKMYT1AR miR-485-5p PKMYT1 Non-small cell lung cancer Cancer stem cells (CSCs) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/830604b3b4b24059a47fea290da65c01
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spelling	oai:doaj.org-article:830604b3b4b24059a47fea290da65c012021-12-05T12:03:26ZLncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway10.1186/s12943-021-01469-61476-4598https://doaj.org/article/830604b3b4b24059a47fea290da65c012021-12-01T00:00:00Zhttps://doi.org/10.1186/s12943-021-01469-6https://doaj.org/toc/1476-4598Abstract Background Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved. Methods Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC. Real-time RT-PCR experiments were used to examine the expression pattern of lncRNA PKMYT1AR, miR-485-5p. Both in vitro and in vivo functional assays were performed to investigate the functional role of PKMYT1AR/miR-485-5p/PKMYT1 axis on regulating cell proliferation, migration and tumor growth. Dual luciferase reporter assay, fluorescent in situ hybridization (FISH), immunoblot, co-immunoprecipitation experiments were used to verify the molecular mechanism. Result Here, we identify a human-specific long non-coding RNA (lncRNA, ENST00000595422), termed PKMYT1AR (PKMYT1 associated lncRNA), that is induced in NSCLC by Yin Yang 1 (YY1) factor, especially in cancerous cell lines (H358, H1975, H1299, H1650, A549 and SPC-A1) compared to that in normal human bronchial epithelium cell line (BEAS-2B). We show that PKMYT1AR high expression correlates with worse clinical outcome, and knockdown of PKMYT1AR inhibits tumor cell proliferation, migration and xenograft tumor formation abilities. Bioinformatic analysis and a luciferase assay demonstrate that PKMYT1AR directly interacts with miR-485-5p to attenuate the inhibitory role on its downstream oncogenic factor PKMYT1 (the protein kinase, membrane-associated tyrosine/threonine 1) in NSCLC. Furthermore, we uncover that miR-485-5p is downregulated in both cancerous cell lines and peripheral blood serum isolated from NSCLC patients compared to reciprocal control groups. Consistently, forced expression of miR-485-5p inhibits the proliferation and migration abilities of tumor cells. Moreover, we provide evidence showing that PKMYT1AR targeting antisense oligonucleotide (ASO) dramatically inhibit tumor growth in vivo. Mechanistic study shows that PKMYT1AR/ miR-485-5p /PKMYT1 axis promotes cancer stem cells (CSCs) maintenance in NSCLC via inhibiting β-TrCP1 mediated ubiquitin degradation of β-catenin proteins, which in turn causes enhanced tumorigenesis. Conclusions Our findings reveal the critical role of PKMYT1AR/miR-485-5p /PKMYT1 axis during NSCLC progression, which could be used as novel therapeutic targets in the future.Yaomei HeXiulin JiangLincan DuanQiuxia XiongYixiao YuanPeishen LiuLiping JiangQiushuo ShenSong ZhaoCuiping YangYongbin ChenBMCarticlePKMYT1ARmiR-485-5pPKMYT1Non-small cell lung cancerCancer stem cells (CSCs)Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Cancer, Vol 20, Iss 1, Pp 1-21 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PKMYT1AR miR-485-5p PKMYT1 Non-small cell lung cancer Cancer stem cells (CSCs) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	PKMYT1AR miR-485-5p PKMYT1 Non-small cell lung cancer Cancer stem cells (CSCs) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yaomei He Xiulin Jiang Lincan Duan Qiuxia Xiong Yixiao Yuan Peishen Liu Liping Jiang Qiushuo Shen Song Zhao Cuiping Yang Yongbin Chen LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway
description	Abstract Background Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved. Methods Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC. Real-time RT-PCR experiments were used to examine the expression pattern of lncRNA PKMYT1AR, miR-485-5p. Both in vitro and in vivo functional assays were performed to investigate the functional role of PKMYT1AR/miR-485-5p/PKMYT1 axis on regulating cell proliferation, migration and tumor growth. Dual luciferase reporter assay, fluorescent in situ hybridization (FISH), immunoblot, co-immunoprecipitation experiments were used to verify the molecular mechanism. Result Here, we identify a human-specific long non-coding RNA (lncRNA, ENST00000595422), termed PKMYT1AR (PKMYT1 associated lncRNA), that is induced in NSCLC by Yin Yang 1 (YY1) factor, especially in cancerous cell lines (H358, H1975, H1299, H1650, A549 and SPC-A1) compared to that in normal human bronchial epithelium cell line (BEAS-2B). We show that PKMYT1AR high expression correlates with worse clinical outcome, and knockdown of PKMYT1AR inhibits tumor cell proliferation, migration and xenograft tumor formation abilities. Bioinformatic analysis and a luciferase assay demonstrate that PKMYT1AR directly interacts with miR-485-5p to attenuate the inhibitory role on its downstream oncogenic factor PKMYT1 (the protein kinase, membrane-associated tyrosine/threonine 1) in NSCLC. Furthermore, we uncover that miR-485-5p is downregulated in both cancerous cell lines and peripheral blood serum isolated from NSCLC patients compared to reciprocal control groups. Consistently, forced expression of miR-485-5p inhibits the proliferation and migration abilities of tumor cells. Moreover, we provide evidence showing that PKMYT1AR targeting antisense oligonucleotide (ASO) dramatically inhibit tumor growth in vivo. Mechanistic study shows that PKMYT1AR/ miR-485-5p /PKMYT1 axis promotes cancer stem cells (CSCs) maintenance in NSCLC via inhibiting β-TrCP1 mediated ubiquitin degradation of β-catenin proteins, which in turn causes enhanced tumorigenesis. Conclusions Our findings reveal the critical role of PKMYT1AR/miR-485-5p /PKMYT1 axis during NSCLC progression, which could be used as novel therapeutic targets in the future.
format	article
author	Yaomei He Xiulin Jiang Lincan Duan Qiuxia Xiong Yixiao Yuan Peishen Liu Liping Jiang Qiushuo Shen Song Zhao Cuiping Yang Yongbin Chen
author_facet	Yaomei He Xiulin Jiang Lincan Duan Qiuxia Xiong Yixiao Yuan Peishen Liu Liping Jiang Qiushuo Shen Song Zhao Cuiping Yang Yongbin Chen
author_sort	Yaomei He
title	LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway
title_short	LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway
title_full	LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway
title_fullStr	LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway
title_full_unstemmed	LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway
title_sort	lncrna pkmyt1ar promotes cancer stem cell maintenance in non-small cell lung cancer via activating wnt signaling pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/830604b3b4b24059a47fea290da65c01
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LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway

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