Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis

Imatinib is a nontoxic tyrosine kinase inhibitor, used in the treatment of advanced renal cell carcinoma. However, some patients with renal cell carcinoma develop resistance to imatinib. Protein disulfide isomerase family 6 (PDIA6) was involved in the chemo-resistance of lung adenocarcinoma. The eff...

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Autores principales:	Yong Huang, Ping He, Juan Ding
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	pdia6 imatinib-resistant renal cell carcinoma cells wnt3a-fzd1 Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/3de6bb16a5554c21b6d40e3bcbdfd814
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spelling	oai:doaj.org-article:3de6bb16a5554c21b6d40e3bcbdfd8142021-11-17T14:21:59ZProtein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis2165-59792165-598710.1080/21655979.2021.2005218https://doaj.org/article/3de6bb16a5554c21b6d40e3bcbdfd8142021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2005218https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Imatinib is a nontoxic tyrosine kinase inhibitor, used in the treatment of advanced renal cell carcinoma. However, some patients with renal cell carcinoma develop resistance to imatinib. Protein disulfide isomerase family 6 (PDIA6) was involved in the chemo-resistance of lung adenocarcinoma. The effect of PDIA6 on imatinib-resistance of renal cell carcinoma was investigated in this study. Firstly, PDIA6 was found to be up-regulated in the imatinib-resistant renal cell carcinoma tissues and cells. Functional assays showed that knockdown of PDIA6 sensitized imatinib-resistant renal cell carcinoma cells to imatinib through decreasing the half-maximal inhibitory concentration (IC50) of imatinib-resistant renal cell carcinoma cells. Secondly, cell proliferation of imatinib-resistant renal cell carcinoma cells was suppressed by PDIA6 silencing, and the apoptosis was promoted with reduced Bcl-2, enhanced Bax and cleaved caspase-3. Moreover, interference of PDIA6 increased phosphorylation of H2A histone family member X (γH2AX), while decreased Rad51 and phosphorylated DNA-dependent protein kinase (DNA-PK) (p-DNA-PK) in imatinib-resistant renal cell carcinoma cells. Lastly, protein expression levels of Wnt3a and Frizzled1 (FZD1) in imatinib-resistant renal cell carcinoma cells were down-regulated by silencing of PDIA6. Over-expression of FZD1 attenuated PDIA6 silencing-induced increase in cell apoptosis and decrease in cell proliferation in imatinib-resistant renal cell carcinoma cells. In conclusion, knockdown of PDIA6 sensitized imatinib-resistant renal cell carcinoma cells to imatinib through inactivation of Wnt3a-FZD1 axis.Yong HuangPing HeJuan DingTaylor & Francis Grouparticlepdia6imatinib-resistantrenal cell carcinoma cellswnt3a-fzd1BiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pdia6 imatinib-resistant renal cell carcinoma cells wnt3a-fzd1 Biotechnology TP248.13-248.65
spellingShingle	pdia6 imatinib-resistant renal cell carcinoma cells wnt3a-fzd1 Biotechnology TP248.13-248.65 Yong Huang Ping He Juan Ding Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis
description	Imatinib is a nontoxic tyrosine kinase inhibitor, used in the treatment of advanced renal cell carcinoma. However, some patients with renal cell carcinoma develop resistance to imatinib. Protein disulfide isomerase family 6 (PDIA6) was involved in the chemo-resistance of lung adenocarcinoma. The effect of PDIA6 on imatinib-resistance of renal cell carcinoma was investigated in this study. Firstly, PDIA6 was found to be up-regulated in the imatinib-resistant renal cell carcinoma tissues and cells. Functional assays showed that knockdown of PDIA6 sensitized imatinib-resistant renal cell carcinoma cells to imatinib through decreasing the half-maximal inhibitory concentration (IC50) of imatinib-resistant renal cell carcinoma cells. Secondly, cell proliferation of imatinib-resistant renal cell carcinoma cells was suppressed by PDIA6 silencing, and the apoptosis was promoted with reduced Bcl-2, enhanced Bax and cleaved caspase-3. Moreover, interference of PDIA6 increased phosphorylation of H2A histone family member X (γH2AX), while decreased Rad51 and phosphorylated DNA-dependent protein kinase (DNA-PK) (p-DNA-PK) in imatinib-resistant renal cell carcinoma cells. Lastly, protein expression levels of Wnt3a and Frizzled1 (FZD1) in imatinib-resistant renal cell carcinoma cells were down-regulated by silencing of PDIA6. Over-expression of FZD1 attenuated PDIA6 silencing-induced increase in cell apoptosis and decrease in cell proliferation in imatinib-resistant renal cell carcinoma cells. In conclusion, knockdown of PDIA6 sensitized imatinib-resistant renal cell carcinoma cells to imatinib through inactivation of Wnt3a-FZD1 axis.
format	article
author	Yong Huang Ping He Juan Ding
author_facet	Yong Huang Ping He Juan Ding
author_sort	Yong Huang
title	Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis
title_short	Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis
title_full	Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis
title_fullStr	Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis
title_full_unstemmed	Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis
title_sort	protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of wnt3a-frizzled1 axis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/3de6bb16a5554c21b6d40e3bcbdfd814
work_keys_str_mv	AT yonghuang proteindisulfideisomerasefamily6promotestheimatinibresistanceofrenalcellcarcinomabyregulationofwnt3afrizzled1axis AT pinghe proteindisulfideisomerasefamily6promotestheimatinibresistanceofrenalcellcarcinomabyregulationofwnt3afrizzled1axis AT juanding proteindisulfideisomerasefamily6promotestheimatinibresistanceofrenalcellcarcinomabyregulationofwnt3afrizzled1axis
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Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis

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