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circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637

BACKGROUND: Resistance to oxaliplatin-based chemotherapy is a major cause of recurrence in colorectal cancer (CRC) patients. There is increasing evidence indicating that circHIPK3 is involved in the development and progression of tumours. However, little is known about the potential role of circHIPK...

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Autores principales: Zhang, Yanli, Li, Chen, Liu, Xinfeng, Wang, Yanlei, Zhao, Rui, Yang, Yongmei, Zheng, Xin, Zhang, Yi, Zhang, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838436/
https://www.ncbi.nlm.nih.gov/pubmed/31631038
http://dx.doi.org/10.1016/j.ebiom.2019.09.051
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author Zhang, Yanli
Li, Chen
Liu, Xinfeng
Wang, Yanlei
Zhao, Rui
Yang, Yongmei
Zheng, Xin
Zhang, Yi
Zhang, Xin
author_facet Zhang, Yanli
Li, Chen
Liu, Xinfeng
Wang, Yanlei
Zhao, Rui
Yang, Yongmei
Zheng, Xin
Zhang, Yi
Zhang, Xin
author_sort Zhang, Yanli
collection PubMed
description BACKGROUND: Resistance to oxaliplatin-based chemotherapy is a major cause of recurrence in colorectal cancer (CRC) patients. There is increasing evidence indicating that circHIPK3 is involved in the development and progression of tumours. However, little is known about the potential role of circHIPK3 in CRC chemotherapy and its molecular mechanisms in chemoresistance also remain unclear. METHODS: Quantitative real-time PCR was performed to detect circHIPK3 expression in tissues of 2 cohorts of CRC patients who received oxaliplatin-based chemotherapy. The chemoresistant effects of circHIPK3 were assessed by cell viability, apoptosis, and autophagy assays. The relationship between circHIPK3, miR-637, and STAT3 mRNA was confirmed by biotinylated RNA pull-down, luciferase reporter, and western blot assays. FINDINGS: In the pilot study, increased circHIPK3 expression was observed in chemoresistant CRC patients. Functional assays showed that circHIPK3 promoted oxaliplatin resistance, which was dependent on inhibition of autophagy. Mechanistically, circHIPK3 sponged miR-637 to promote STAT3 expression, thereby activating the downstream Bcl-2/beclin1 signalling pathway. A clinical cohort study showed that circHIPK3 was upregulated in tissues from recurrent CRC patients and correlated with tumour size, regional lymph node metastasis, distant metastasis, and survival. INTERPRETATION: circHIPK3 functions as a chemoresistant gene in CRC cells by targeting the miR-637/STAT3/Bcl-2/beclin1 axis and might be a prognostic predictor for CRC patients who receive oxaliplatin-based chemotherapy. FUNDING: National Natural Science Foundation of China (81301506), Shandong Medical and Health Technology Development Project(2018WSB20002), Shandong Key Research and Development Program (2016GSF201122), Natural Science Foundation of Shandong Province (ZR2017MH044), and Jinan Science and Technology Development Plan(201805084, 201805003).
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spelling pubmed-68384362019-11-12 circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637 Zhang, Yanli Li, Chen Liu, Xinfeng Wang, Yanlei Zhao, Rui Yang, Yongmei Zheng, Xin Zhang, Yi Zhang, Xin EBioMedicine Research paper BACKGROUND: Resistance to oxaliplatin-based chemotherapy is a major cause of recurrence in colorectal cancer (CRC) patients. There is increasing evidence indicating that circHIPK3 is involved in the development and progression of tumours. However, little is known about the potential role of circHIPK3 in CRC chemotherapy and its molecular mechanisms in chemoresistance also remain unclear. METHODS: Quantitative real-time PCR was performed to detect circHIPK3 expression in tissues of 2 cohorts of CRC patients who received oxaliplatin-based chemotherapy. The chemoresistant effects of circHIPK3 were assessed by cell viability, apoptosis, and autophagy assays. The relationship between circHIPK3, miR-637, and STAT3 mRNA was confirmed by biotinylated RNA pull-down, luciferase reporter, and western blot assays. FINDINGS: In the pilot study, increased circHIPK3 expression was observed in chemoresistant CRC patients. Functional assays showed that circHIPK3 promoted oxaliplatin resistance, which was dependent on inhibition of autophagy. Mechanistically, circHIPK3 sponged miR-637 to promote STAT3 expression, thereby activating the downstream Bcl-2/beclin1 signalling pathway. A clinical cohort study showed that circHIPK3 was upregulated in tissues from recurrent CRC patients and correlated with tumour size, regional lymph node metastasis, distant metastasis, and survival. INTERPRETATION: circHIPK3 functions as a chemoresistant gene in CRC cells by targeting the miR-637/STAT3/Bcl-2/beclin1 axis and might be a prognostic predictor for CRC patients who receive oxaliplatin-based chemotherapy. FUNDING: National Natural Science Foundation of China (81301506), Shandong Medical and Health Technology Development Project(2018WSB20002), Shandong Key Research and Development Program (2016GSF201122), Natural Science Foundation of Shandong Province (ZR2017MH044), and Jinan Science and Technology Development Plan(201805084, 201805003). Elsevier 2019-10-17 /pmc/articles/PMC6838436/ /pubmed/31631038 http://dx.doi.org/10.1016/j.ebiom.2019.09.051 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Zhang, Yanli
Li, Chen
Liu, Xinfeng
Wang, Yanlei
Zhao, Rui
Yang, Yongmei
Zheng, Xin
Zhang, Yi
Zhang, Xin
circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637
title circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637
title_full circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637
title_fullStr circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637
title_full_unstemmed circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637
title_short circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637
title_sort circhipk3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging mir-637
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838436/
https://www.ncbi.nlm.nih.gov/pubmed/31631038
http://dx.doi.org/10.1016/j.ebiom.2019.09.051
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