HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer

HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer

Objective. To discover the correlated gene with HEATR1 in regulating chemoresistance of gemcitabine. Methods. Gene chip analysis was performed to find out differential genes between HEATR1-KD and control groups. The top 20 genes were subjected to high-content screening, and functional assay was impl...

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Main Authors: Yuan Fang, Xu Han, Jianang Li, Tiantao Kuang, Wenhui Lou
Format: Article
Language:English
Published: Hindawi Limited 2020-01-01
Series:Journal of Oncology
Online Access:http://dx.doi.org/10.1155/2020/3181596
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spelling doaj-b2c11eca5e40473ab087dda400458ade2020-11-25T03:29:10ZengHindawi LimitedJournal of Oncology1687-84501687-84692020-01-01202010.1155/2020/31815963181596HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic CancerYuan Fang0Xu Han1Jianang Li2Tiantao Kuang3Wenhui Lou4Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaObjective. To discover the correlated gene with HEATR1 in regulating chemoresistance of gemcitabine. Methods. Gene chip analysis was performed to find out differential genes between HEATR1-KD and control groups. The top 20 genes were subjected to high-content screening, and functional assay was implemented. Gene expression profiling was carried out to find the downstream target. Immunohistochemistry and survival analysis were performed. Results. ZNF185 fold change (4.5285) was the most significant between the HEATR1-KD and control groups. Knocking down ZNF185 could promote the chemosensitivity, apoptosis, and proliferative inhibition, with SMAD4 significantly upregulated. Patients with high HEATR1 and SMAD4 or low ZNF185 exhibited better survival. Conclusion. HEATR1, ZNF185, and SMAD4 could affect the chemosensitivity of gemcitabine and may be the indicators of gemcitabine selection in the chemotherapy of pancreatic cancer.http://dx.doi.org/10.1155/2020/3181596
collection DOAJ
language English
format Article
sources DOAJ
author Yuan Fang
Xu Han
Jianang Li
Tiantao Kuang
Wenhui Lou
spellingShingle Yuan Fang
Xu Han
Jianang Li
Tiantao Kuang
Wenhui Lou
HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer
Journal of Oncology
author_facet Yuan Fang
Xu Han
Jianang Li
Tiantao Kuang
Wenhui Lou
author_sort Yuan Fang
title HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer
title_short HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer
title_full HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer
title_fullStr HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer
title_full_unstemmed HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer
title_sort heatr1 deficiency promotes chemoresistance via upregulating znf185 and downregulating smad4 in pancreatic cancer
publisher Hindawi Limited
series Journal of Oncology
issn 1687-8450
1687-8469
publishDate 2020-01-01
description Objective. To discover the correlated gene with HEATR1 in regulating chemoresistance of gemcitabine. Methods. Gene chip analysis was performed to find out differential genes between HEATR1-KD and control groups. The top 20 genes were subjected to high-content screening, and functional assay was implemented. Gene expression profiling was carried out to find the downstream target. Immunohistochemistry and survival analysis were performed. Results. ZNF185 fold change (4.5285) was the most significant between the HEATR1-KD and control groups. Knocking down ZNF185 could promote the chemosensitivity, apoptosis, and proliferative inhibition, with SMAD4 significantly upregulated. Patients with high HEATR1 and SMAD4 or low ZNF185 exhibited better survival. Conclusion. HEATR1, ZNF185, and SMAD4 could affect the chemosensitivity of gemcitabine and may be the indicators of gemcitabine selection in the chemotherapy of pancreatic cancer.
url http://dx.doi.org/10.1155/2020/3181596
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AT xuhan heatr1deficiencypromoteschemoresistanceviaupregulatingznf185anddownregulatingsmad4inpancreaticcancer
AT jianangli heatr1deficiencypromoteschemoresistanceviaupregulatingznf185anddownregulatingsmad4inpancreaticcancer
AT tiantaokuang heatr1deficiencypromoteschemoresistanceviaupregulatingznf185anddownregulatingsmad4inpancreaticcancer
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