Long noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p

Abstract Background The emergence of chemoresistance to 5-fluorouracil (5-FU)-based chemotherapy is the main cause of treatment failure in advanced and metastatic colorectal cancer (CRC) patients. Long noncoding RNAs (lncRNAs) have been reported to be involved in 5-FU resistance. Previously, we firs...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jingui Wang, Xiaoqian Zhang, Junling Zhang, Shangwen Chen, Jing Zhu, Xin Wang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Long noncoding RNA CRART16 5-FU Resistance miR-193b-5p HMGA2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/1795441c8875475caf74e4b1627d81da
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1795441c8875475caf74e4b1627d81da
record_format	dspace
spelling	oai:doaj.org-article:1795441c8875475caf74e4b1627d81da2021-12-05T12:23:40ZLong noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p10.1186/s12935-021-02353-51475-2867https://doaj.org/article/1795441c8875475caf74e4b1627d81da2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02353-5https://doaj.org/toc/1475-2867Abstract Background The emergence of chemoresistance to 5-fluorouracil (5-FU)-based chemotherapy is the main cause of treatment failure in advanced and metastatic colorectal cancer (CRC) patients. Long noncoding RNAs (lncRNAs) have been reported to be involved in 5-FU resistance. Previously, we first detected that lncRNA cetuximab resistance-associated RNA transcript 16 (CRART16) could contribute to cetuximab resistance by upregulating V-Erb-B2 erythroblastic leukemia viral oncogene homologue 3 (ERBB3) expression by sponging miR-371a-5p in CRC cells. The current study aimed to explore the role of CRART16 in acquired 5-FU resistance in CRC cells and its possible mechanism. Methods Quantitative real-time PCR (RT-qPCR) was used to measure the expression levels of CRART16 in a 5-FU-resistant CRC cell subline (SW620/5-FU) and the parent cell line. Lentivirus transduction was performed to establish SW620 and Caco-2 cells stably overexpressing CRART16. Cell Counting Kit-8 (CCK-8) assays and colony formation assays were applied to measure cell chemosensitivity to 5-FU. Flow cytometric and immunofluorescence staining were adopted to assess cell apoptosis induced by 5-FU. The dual-luciferase reporter assay was used to validate the direct interactions between CRART16 and miR-193b-5p and between miR-193b-5p and high-mobility group AT-hook-2 (HMGA2). The expression levels of HMGA2, apoptosis-associated proteins and p-ERK were examined by western blotting. The statistical differences within any two groups were used Student’s t test. Results CRART16 was upregulated in SW620/5-FU cells. Overexpression of CRART16 reduced the sensitivity of CRC cells to 5-FU by attenuating apoptosis. In addition, CRART16 promoted 5-FU resistance by suppressing the expression of miR-193b-5p. Furthermore, CRART16 modulated the expression of HMGA2 by inhibiting miR-193b-5p and activated the MAPK signaling pathway. Conclusions CRART16 confers 5-FU resistance in CRC cells through the CRART16/miR-193b-5p/HMGA2/MAPK pathway.Jingui WangXiaoqian ZhangJunling ZhangShangwen ChenJing ZhuXin WangBMCarticleLong noncoding RNACRART165-FUResistancemiR-193b-5pHMGA2Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Long noncoding RNA CRART16 5-FU Resistance miR-193b-5p HMGA2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Long noncoding RNA CRART16 5-FU Resistance miR-193b-5p HMGA2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Jingui Wang Xiaoqian Zhang Junling Zhang Shangwen Chen Jing Zhu Xin Wang Long noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p
description	Abstract Background The emergence of chemoresistance to 5-fluorouracil (5-FU)-based chemotherapy is the main cause of treatment failure in advanced and metastatic colorectal cancer (CRC) patients. Long noncoding RNAs (lncRNAs) have been reported to be involved in 5-FU resistance. Previously, we first detected that lncRNA cetuximab resistance-associated RNA transcript 16 (CRART16) could contribute to cetuximab resistance by upregulating V-Erb-B2 erythroblastic leukemia viral oncogene homologue 3 (ERBB3) expression by sponging miR-371a-5p in CRC cells. The current study aimed to explore the role of CRART16 in acquired 5-FU resistance in CRC cells and its possible mechanism. Methods Quantitative real-time PCR (RT-qPCR) was used to measure the expression levels of CRART16 in a 5-FU-resistant CRC cell subline (SW620/5-FU) and the parent cell line. Lentivirus transduction was performed to establish SW620 and Caco-2 cells stably overexpressing CRART16. Cell Counting Kit-8 (CCK-8) assays and colony formation assays were applied to measure cell chemosensitivity to 5-FU. Flow cytometric and immunofluorescence staining were adopted to assess cell apoptosis induced by 5-FU. The dual-luciferase reporter assay was used to validate the direct interactions between CRART16 and miR-193b-5p and between miR-193b-5p and high-mobility group AT-hook-2 (HMGA2). The expression levels of HMGA2, apoptosis-associated proteins and p-ERK were examined by western blotting. The statistical differences within any two groups were used Student’s t test. Results CRART16 was upregulated in SW620/5-FU cells. Overexpression of CRART16 reduced the sensitivity of CRC cells to 5-FU by attenuating apoptosis. In addition, CRART16 promoted 5-FU resistance by suppressing the expression of miR-193b-5p. Furthermore, CRART16 modulated the expression of HMGA2 by inhibiting miR-193b-5p and activated the MAPK signaling pathway. Conclusions CRART16 confers 5-FU resistance in CRC cells through the CRART16/miR-193b-5p/HMGA2/MAPK pathway.
format	article
author	Jingui Wang Xiaoqian Zhang Junling Zhang Shangwen Chen Jing Zhu Xin Wang
author_facet	Jingui Wang Xiaoqian Zhang Junling Zhang Shangwen Chen Jing Zhu Xin Wang
author_sort	Jingui Wang
title	Long noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p
title_short	Long noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p
title_full	Long noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p
title_fullStr	Long noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p
title_full_unstemmed	Long noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p
title_sort	long noncoding rna crart16 confers 5-fu resistance in colorectal cancer cells by sponging mir-193b-5p
publisher	BMC
publishDate	2021
url	https://doaj.org/article/1795441c8875475caf74e4b1627d81da
work_keys_str_mv	AT jinguiwang longnoncodingrnacrart16confers5furesistanceincolorectalcancercellsbyspongingmir193b5p AT xiaoqianzhang longnoncodingrnacrart16confers5furesistanceincolorectalcancercellsbyspongingmir193b5p AT junlingzhang longnoncodingrnacrart16confers5furesistanceincolorectalcancercellsbyspongingmir193b5p AT shangwenchen longnoncodingrnacrart16confers5furesistanceincolorectalcancercellsbyspongingmir193b5p AT jingzhu longnoncodingrnacrart16confers5furesistanceincolorectalcancercellsbyspongingmir193b5p AT xinwang longnoncodingrnacrart16confers5furesistanceincolorectalcancercellsbyspongingmir193b5p
_version_	1718371943971815424

Long noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p

Ejemplares similares