Cargando…

CircCRIM1 promotes ovarian cancer progression by working as ceRNAs of CRIM1 and targeting miR-383-5p/ZEB2 axis

BACKGROUND: Ovarian cancer is the leading cause of death in patients with gynecologic cancer, and circular RNAs (circRNAs) are involved in cancer progression. However, there are limited studies on the roles of circRNAs in ovarian cancer. METHODS: We designed divergent and convergent primers, used sa...

Descripción completa

Detalles Bibliográficos
Autores principales: Du, Yuping, Liu, Xin, Zhang, Song, Chen, Shuo, Guan, Xue, Li, Qianhui, Chen, Xi, Zhao, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630901/
https://www.ncbi.nlm.nih.gov/pubmed/34847936
http://dx.doi.org/10.1186/s12958-021-00857-3
_version_ 1784607453145464832
author Du, Yuping
Liu, Xin
Zhang, Song
Chen, Shuo
Guan, Xue
Li, Qianhui
Chen, Xi
Zhao, Yang
author_facet Du, Yuping
Liu, Xin
Zhang, Song
Chen, Shuo
Guan, Xue
Li, Qianhui
Chen, Xi
Zhao, Yang
author_sort Du, Yuping
collection PubMed
description BACKGROUND: Ovarian cancer is the leading cause of death in patients with gynecologic cancer, and circular RNAs (circRNAs) are involved in cancer progression. However, there are limited studies on the roles of circRNAs in ovarian cancer. METHODS: We designed divergent and convergent primers, used sanger sequencing and RNase R digestion to verify the source of circCRIM1. We detected the expression of circCRIM1 and its parental gene cysteine rich transmembrane BMP regulator 1 (CRIM1) in ovarian cancer and normal ovarian samples via qRT-PCR. MTT viability assay, apoptosis assay, wound healing assay and invasion assay were used to investigate the function of circCRIM1 and CRIM1 in ovarian cancer cell lines OVCAR3 and CAOV3. Mice xenografts experiment was performed. Bioinformatics predicted the microRNAs that bond with circCRIM1 and CRIM1, and dual luciferase reporter system confirmed it. Rescue experiments of microRNAs mimics transfection on the basis of circCRIM1 over-expression were carried out to uncover the mechanism by which circCRIM1 played cancer-promoting roles in ovarian cancer. RESULTS: CircCRIM1 was derived from CRIM1 by back-splicing. CircCRIM1 and CRIM1 had higher expression in ovarian cancer than in normal ovarian tissues, and both of them promoted ovarian cancer progression in vitro. In vivo circCRIM1 promoted the growth of tumors. CircCRIM1 and CRIM1 had a positive correlation relationship in the same cohort of ovarian cancer tissues. Bioinformatics predicted and dual luciferase assay confirmed circCRIM1 and CRIM1 bond with miR-145-5p, and circCRIM1 bond with miR-383-5p additionally. CircCRIM1 positively affected the expression of CRIM1. After circCRIM1 was over-expressed, miR-145-5p mimics transfection reversed the expression of CRIM1. Western blot discovered circCRIM1 positively affected the expression of zinc finger E-box binding homeobox 2 (ZEB2). Rescue experiments found miR-383-5p mimics reversed ZEB2 expression and the cancer-promoting effects of circCRIM1. CONCLUSIONS: CircCRIM1 bond with miR-145-5p to work as competing endogenous RNA (ceRNA) of CRIM1, and circCRIM1 bond with miR-383-5p to improve the expression of ZEB2 in ovarian cancer. CircCRIM1 and CRIM1 promoted the ovarian cancer progression and supplied a novel insight into the researches of ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12958-021-00857-3.
format Online
Article
Text
id pubmed-8630901
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-86309012021-12-01 CircCRIM1 promotes ovarian cancer progression by working as ceRNAs of CRIM1 and targeting miR-383-5p/ZEB2 axis Du, Yuping Liu, Xin Zhang, Song Chen, Shuo Guan, Xue Li, Qianhui Chen, Xi Zhao, Yang Reprod Biol Endocrinol Research BACKGROUND: Ovarian cancer is the leading cause of death in patients with gynecologic cancer, and circular RNAs (circRNAs) are involved in cancer progression. However, there are limited studies on the roles of circRNAs in ovarian cancer. METHODS: We designed divergent and convergent primers, used sanger sequencing and RNase R digestion to verify the source of circCRIM1. We detected the expression of circCRIM1 and its parental gene cysteine rich transmembrane BMP regulator 1 (CRIM1) in ovarian cancer and normal ovarian samples via qRT-PCR. MTT viability assay, apoptosis assay, wound healing assay and invasion assay were used to investigate the function of circCRIM1 and CRIM1 in ovarian cancer cell lines OVCAR3 and CAOV3. Mice xenografts experiment was performed. Bioinformatics predicted the microRNAs that bond with circCRIM1 and CRIM1, and dual luciferase reporter system confirmed it. Rescue experiments of microRNAs mimics transfection on the basis of circCRIM1 over-expression were carried out to uncover the mechanism by which circCRIM1 played cancer-promoting roles in ovarian cancer. RESULTS: CircCRIM1 was derived from CRIM1 by back-splicing. CircCRIM1 and CRIM1 had higher expression in ovarian cancer than in normal ovarian tissues, and both of them promoted ovarian cancer progression in vitro. In vivo circCRIM1 promoted the growth of tumors. CircCRIM1 and CRIM1 had a positive correlation relationship in the same cohort of ovarian cancer tissues. Bioinformatics predicted and dual luciferase assay confirmed circCRIM1 and CRIM1 bond with miR-145-5p, and circCRIM1 bond with miR-383-5p additionally. CircCRIM1 positively affected the expression of CRIM1. After circCRIM1 was over-expressed, miR-145-5p mimics transfection reversed the expression of CRIM1. Western blot discovered circCRIM1 positively affected the expression of zinc finger E-box binding homeobox 2 (ZEB2). Rescue experiments found miR-383-5p mimics reversed ZEB2 expression and the cancer-promoting effects of circCRIM1. CONCLUSIONS: CircCRIM1 bond with miR-145-5p to work as competing endogenous RNA (ceRNA) of CRIM1, and circCRIM1 bond with miR-383-5p to improve the expression of ZEB2 in ovarian cancer. CircCRIM1 and CRIM1 promoted the ovarian cancer progression and supplied a novel insight into the researches of ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12958-021-00857-3. BioMed Central 2021-11-30 /pmc/articles/PMC8630901/ /pubmed/34847936 http://dx.doi.org/10.1186/s12958-021-00857-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Du, Yuping
Liu, Xin
Zhang, Song
Chen, Shuo
Guan, Xue
Li, Qianhui
Chen, Xi
Zhao, Yang
CircCRIM1 promotes ovarian cancer progression by working as ceRNAs of CRIM1 and targeting miR-383-5p/ZEB2 axis
title CircCRIM1 promotes ovarian cancer progression by working as ceRNAs of CRIM1 and targeting miR-383-5p/ZEB2 axis
title_full CircCRIM1 promotes ovarian cancer progression by working as ceRNAs of CRIM1 and targeting miR-383-5p/ZEB2 axis
title_fullStr CircCRIM1 promotes ovarian cancer progression by working as ceRNAs of CRIM1 and targeting miR-383-5p/ZEB2 axis
title_full_unstemmed CircCRIM1 promotes ovarian cancer progression by working as ceRNAs of CRIM1 and targeting miR-383-5p/ZEB2 axis
title_short CircCRIM1 promotes ovarian cancer progression by working as ceRNAs of CRIM1 and targeting miR-383-5p/ZEB2 axis
title_sort circcrim1 promotes ovarian cancer progression by working as cernas of crim1 and targeting mir-383-5p/zeb2 axis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630901/
https://www.ncbi.nlm.nih.gov/pubmed/34847936
http://dx.doi.org/10.1186/s12958-021-00857-3
work_keys_str_mv AT duyuping circcrim1promotesovariancancerprogressionbyworkingascernasofcrim1andtargetingmir3835pzeb2axis
AT liuxin circcrim1promotesovariancancerprogressionbyworkingascernasofcrim1andtargetingmir3835pzeb2axis
AT zhangsong circcrim1promotesovariancancerprogressionbyworkingascernasofcrim1andtargetingmir3835pzeb2axis
AT chenshuo circcrim1promotesovariancancerprogressionbyworkingascernasofcrim1andtargetingmir3835pzeb2axis
AT guanxue circcrim1promotesovariancancerprogressionbyworkingascernasofcrim1andtargetingmir3835pzeb2axis
AT liqianhui circcrim1promotesovariancancerprogressionbyworkingascernasofcrim1andtargetingmir3835pzeb2axis
AT chenxi circcrim1promotesovariancancerprogressionbyworkingascernasofcrim1andtargetingmir3835pzeb2axis
AT zhaoyang circcrim1promotesovariancancerprogressionbyworkingascernasofcrim1andtargetingmir3835pzeb2axis