RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis

Abstract Background Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved. Methods Expression of circ_0000745 in collected OC tissues and t...

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Autores principales:	Shengtan Wang, Zaihong Li, Genhai Zhu, Lan Hong, Chunyan Hu, Kang Wang, Kaiying Cui, Chunbo Hao
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Ovarian cancer IGF2BP2 circ_0000745 miR-3187-3p ERBB4 PI3K/AKT Gynecology and obstetrics RG1-991
Acceso en línea:	https://doaj.org/article/e1a6d3ccbb914c019dddc850b358e9e8
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spelling	oai:doaj.org-article:e1a6d3ccbb914c019dddc850b358e9e82021-11-14T12:32:00ZRNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis10.1186/s13048-021-00917-71757-2215https://doaj.org/article/e1a6d3ccbb914c019dddc850b358e9e82021-11-01T00:00:00Zhttps://doi.org/10.1186/s13048-021-00917-7https://doaj.org/toc/1757-2215Abstract Background Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved. Methods Expression of circ_0000745 in collected OC tissues and the acquired OC cell lines was examined by RT-qPCR. The stability of circ_0000745 in cells was examined by RNase R treatment. The target transcripts interacted with circ_0000745 were predicted using bioinformatic systems. Gain- and loss-of-function studies of circ_0000745, microRNA (miR)-3187-3p and erb-b2 receptor tyrosine kinase 4 (ERBB4) were conducted to determine their functions on proliferation, migration, invasion and stem cell property of OC cells. Results Circ_0000745 and ERBB4 were abundantly expressed while miR-3187-3p was poorly expressed in OC tissues and cells. Circ_0000745 sequestered miR-3187-3p and blocked its repressive effect on ERBB4. Downregulation of circ_0000745 reduced proliferation, aggressiveness, epithelial-mesenchymal transition, and stemness of SK-OV-3 cells, but this reduction was blocked upon miR-3187-3p inhibition or ERBB4 upregulation. By contrast, artificial induction of circ_0000745 upregulation, miR-3187-3p upregulation and ERBB4 downregulation led to inverse trends in ES-2 cells. ERBB4 promoted the phosphorylation of the PI3K/AKT signaling pathway. An RNA binding protein IGF2BP2 was found to circ_0000745 bind to and promote its expression and stability. Conclusion This study demonstrated that circ_0000745 upregulated by IGF2BP2 promotes aggressiveness and stemness of OC cells through a miR-3187-3p/ERBB4/PI3K/AKT axis. Circ_0000745 may serve as a promising target for OC treatment.Shengtan WangZaihong LiGenhai ZhuLan HongChunyan HuKang WangKaiying CuiChunbo HaoBMCarticleOvarian cancerIGF2BP2circ_0000745miR-3187-3pERBB4PI3K/AKTGynecology and obstetricsRG1-991ENJournal of Ovarian Research, Vol 14, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ovarian cancer IGF2BP2 circ_0000745 miR-3187-3p ERBB4 PI3K/AKT Gynecology and obstetrics RG1-991
spellingShingle	Ovarian cancer IGF2BP2 circ_0000745 miR-3187-3p ERBB4 PI3K/AKT Gynecology and obstetrics RG1-991 Shengtan Wang Zaihong Li Genhai Zhu Lan Hong Chunyan Hu Kang Wang Kaiying Cui Chunbo Hao RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis
description	Abstract Background Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved. Methods Expression of circ_0000745 in collected OC tissues and the acquired OC cell lines was examined by RT-qPCR. The stability of circ_0000745 in cells was examined by RNase R treatment. The target transcripts interacted with circ_0000745 were predicted using bioinformatic systems. Gain- and loss-of-function studies of circ_0000745, microRNA (miR)-3187-3p and erb-b2 receptor tyrosine kinase 4 (ERBB4) were conducted to determine their functions on proliferation, migration, invasion and stem cell property of OC cells. Results Circ_0000745 and ERBB4 were abundantly expressed while miR-3187-3p was poorly expressed in OC tissues and cells. Circ_0000745 sequestered miR-3187-3p and blocked its repressive effect on ERBB4. Downregulation of circ_0000745 reduced proliferation, aggressiveness, epithelial-mesenchymal transition, and stemness of SK-OV-3 cells, but this reduction was blocked upon miR-3187-3p inhibition or ERBB4 upregulation. By contrast, artificial induction of circ_0000745 upregulation, miR-3187-3p upregulation and ERBB4 downregulation led to inverse trends in ES-2 cells. ERBB4 promoted the phosphorylation of the PI3K/AKT signaling pathway. An RNA binding protein IGF2BP2 was found to circ_0000745 bind to and promote its expression and stability. Conclusion This study demonstrated that circ_0000745 upregulated by IGF2BP2 promotes aggressiveness and stemness of OC cells through a miR-3187-3p/ERBB4/PI3K/AKT axis. Circ_0000745 may serve as a promising target for OC treatment.
format	article
author	Shengtan Wang Zaihong Li Genhai Zhu Lan Hong Chunyan Hu Kang Wang Kaiying Cui Chunbo Hao
author_facet	Shengtan Wang Zaihong Li Genhai Zhu Lan Hong Chunyan Hu Kang Wang Kaiying Cui Chunbo Hao
author_sort	Shengtan Wang
title	RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis
title_short	RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis
title_full	RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis
title_fullStr	RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis
title_full_unstemmed	RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis
title_sort	rna-binding protein igf2bp2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microrna-3187-3p/erbb4/pi3k/akt axis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e1a6d3ccbb914c019dddc850b358e9e8
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RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis

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