CircLMTK2 Silencing Attenuates Gemcitabine Resistance in Pancreatic Cancer by Sponging miR-485-5p and to Target PAK1

Pancreatic cancer (PC) has a high degree of malignancy and poor prognosis, and countless patients have distant metastasis when diagnosed. Gemcitabine (GEM) chemotherapy is one of the main ways of treatment. However, PC cells have been displayed chemoresistance to GEM during treatment. Circular RNAs...

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Published in:Journal of oncology 2022-08, Vol.2022, p.1-12
Main Authors: Lu, Yeting, Zhou, Shuping, Cheng, Gong, Ruan, Yi, Tian, Yuan, Lv, Kaiji, Han, Shuo, Zhou, Xinhua
Format: Article
Language:English
Subjects:
Apoptosis
Cancer
Cancer therapies
Chemotherapy
Datasets
Epigenetics
Gemcitabine
Gene expression
Medical prognosis
MicroRNAs
Pancreatic cancer
Plasmids
Proteins
Software
Statistical analysis
Survival analysis
Wound healing
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container_title Journal of oncology
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Lv, Kaiji
Han, Shuo
Zhou, Xinhua
description Pancreatic cancer (PC) has a high degree of malignancy and poor prognosis, and countless patients have distant metastasis when diagnosed. Gemcitabine (GEM) chemotherapy is one of the main ways of treatment. However, PC cells have been displayed chemoresistance to GEM during treatment. Circular RNAs (circRNAs) have been demonstrated to be the most popular diagnostic and prognostic biomarkers in PC with GEM resistance. Here, we assessed the potential of circLMTK2 in the GEM resistance of PC cells. Functional assays were implemented to measure the impacts of circLMTK2 on the proliferation, migration/invasion, and apoptosis of GEM-resistant PC cells. Bioinformatics analysis and mechanical experiments displayed the underlying mechanism of circLMTK2 in GEM-resistant PC cells. We found that circLMTK2 was upregulated in PC and GEM-resistant PC tissues and cells. CircLMTK2 knockdown suppressed proliferation, invasion, migration, and enhanced apoptosis in GEM-resistant PC cells. Moreover, circLMTK2 silencing could decrease GEM resistance-associated tumor size in vivo. In terms of mechanism, circLMTK2 served as a sponge for miR-485-5p, and miR-485-5p bound to p21 (RAC1) activated kinase 1 (PAK1), which were clarified via the dual-luciferase assay in PC cell lines. We confirmed that circLMTK2 knockdown attenuated GEM-resistant PC cells by regulating PAK1 via miR-485-5p. Our study demonstrated that circLMTK2 may be a novel diagnostic and prognostic biomarker in GEM-resistant PC cells.
doi_str_mv 10.1155/2022/1911592
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Gemcitabine (GEM) chemotherapy is one of the main ways of treatment. However, PC cells have been displayed chemoresistance to GEM during treatment. Circular RNAs (circRNAs) have been demonstrated to be the most popular diagnostic and prognostic biomarkers in PC with GEM resistance. Here, we assessed the potential of circLMTK2 in the GEM resistance of PC cells. Functional assays were implemented to measure the impacts of circLMTK2 on the proliferation, migration/invasion, and apoptosis of GEM-resistant PC cells. Bioinformatics analysis and mechanical experiments displayed the underlying mechanism of circLMTK2 in GEM-resistant PC cells. We found that circLMTK2 was upregulated in PC and GEM-resistant PC tissues and cells. CircLMTK2 knockdown suppressed proliferation, invasion, migration, and enhanced apoptosis in GEM-resistant PC cells. Moreover, circLMTK2 silencing could decrease GEM resistance-associated tumor size in vivo. In terms of mechanism, circLMTK2 served as a sponge for miR-485-5p, and miR-485-5p bound to p21 (RAC1) activated kinase 1 (PAK1), which were clarified via the dual-luciferase assay in PC cell lines. We confirmed that circLMTK2 knockdown attenuated GEM-resistant PC cells by regulating PAK1 via miR-485-5p. Our study demonstrated that circLMTK2 may be a novel diagnostic and prognostic biomarker in GEM-resistant PC cells.</description><identifier>ISSN: 1687-8450</identifier><identifier>EISSN: 1687-8450</identifier><identifier>DOI: 10.1155/2022/1911592</identifier><identifier>PMID: 36059806</identifier><language>eng</language><publisher>New York: Hindawi</publisher><subject>Apoptosis ; Cancer ; Cancer therapies ; Chemotherapy ; Datasets ; Epigenetics ; Gemcitabine ; Gene expression ; Medical prognosis ; MicroRNAs ; Pancreatic cancer ; Plasmids ; Proteins ; Software ; Statistical analysis ; Survival analysis ; Wound healing</subject><ispartof>Journal of oncology, 2022-08, Vol.2022, p.1-12</ispartof><rights>Copyright © 2022 Yeting Lu et al.</rights><rights>COPYRIGHT 2022 John Wiley &amp; Sons, Inc.</rights><rights>Copyright © 2022 Yeting Lu et al. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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subjects Apoptosis
Cancer
Cancer therapies
Chemotherapy
Datasets
Epigenetics
Gemcitabine
Gene expression
Medical prognosis
MicroRNAs
Pancreatic cancer
Plasmids
Proteins
Software
Statistical analysis
Survival analysis
Wound healing
title CircLMTK2 Silencing Attenuates Gemcitabine Resistance in Pancreatic Cancer by Sponging miR-485-5p and to Target PAK1
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