MiR-331-3p Links to Drug Resistance of Pancreatic Cancer Cells by Activating WNT/β-Catenin Signal via ST7L
Background: Pancreatic cancer is an aggressive type of cancer with poor prognosis, short survival rate, and high mortality. Drug resistance is a major cause of treatment failure in the disease. MiR-331-3p has been reported to play an important role in several cancers. We previously showed that miR-3...
Main Authors: | , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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SAGE Publishing
2020-09-01
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Series: | Technology in Cancer Research & Treatment |
Online Access: | https://doi.org/10.1177/1533033820945801 |
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author | Ting Zhan MM Xiaoli Chen MM Xia Tian MM Zheng Han MM Meng Liu PhD Yanli Zou MM Shasha Huang MM Aifang Chen MM Xueting Cheng MM Junsheng Deng MM Jie Tan MM Xiaodong Huang PhD |
author_facet | Ting Zhan MM Xiaoli Chen MM Xia Tian MM Zheng Han MM Meng Liu PhD Yanli Zou MM Shasha Huang MM Aifang Chen MM Xueting Cheng MM Junsheng Deng MM Jie Tan MM Xiaodong Huang PhD |
author_sort | Ting Zhan MM |
collection | DOAJ |
description | Background: Pancreatic cancer is an aggressive type of cancer with poor prognosis, short survival rate, and high mortality. Drug resistance is a major cause of treatment failure in the disease. MiR-331-3p has been reported to play an important role in several cancers. We previously showed that miR-331-3p is upregulated in pancreatic cancer and promotes pancreatic cancer cell proliferation and epithelial-to-mesenchymal transition–mediated metastasis by targeting ST7L. However, it is uncertain whether miR-331-3p is involved in drug resistance. Methods: We investigated the relationship between miR-331-3p and pancreatic cancer drug resistance. As part of this, microRNA mimics or inhibitors were transfected into pancreatic cancer cells. Quantitative polymerase chain reaction was used to detect miR-331-3p expression, and flow cytometry was used to detect cell apoptosis. The Cell Counting Kit-8 assay was used to measure the IC50 values of gemcitabine in pancreatic cancer cells. The expression of multidrug resistance protein 1, multidrug resistance-related protein 1, breast cancer resistance protein, β-Catenin, c-Myc, Cyclin D1, Bcl-2, and Caspase-3 was evaluated by Western blotting. Results: We confirmed that miR-331-3p is upregulated in gemcitabine-treated pancreatic cancer cells and plasma from chemotherapy patients. We also confirmed that miR-331-3p inhibition decreased drug resistance by regulating cell apoptosis and multidrug resistance protein 1, multidrug resistance-related protein 1, and breast cancer resistance protein expression in pancreatic cancer cells, whereas miR-331-3p overexpression had the opposite effect. We further demonstrated that miR-331-3p effects in drug resistance were partially reversed by ST7L overexpression. In addition, overexpression of miR-331-3p activated Wnt/β-catenin signaling in pancreatic cancer cells, and ST7L overexpression restored activation of Wnt/β-catenin signaling. Conclusions: Taken together, our data demonstrate that miR-331-3p contributes to drug resistance by activating Wnt/β-catenin signaling via ST7L in pancreatic cancer cells. These data provide a theoretical basis for new targeted therapies in the future. |
first_indexed | 2024-12-11T06:41:04Z |
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id | doaj.art-ef116c7c8bce45a6908ebd860674617d |
institution | Directory Open Access Journal |
issn | 1533-0338 |
language | English |
last_indexed | 2024-12-11T06:41:04Z |
publishDate | 2020-09-01 |
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series | Technology in Cancer Research & Treatment |
spelling | doaj.art-ef116c7c8bce45a6908ebd860674617d2022-12-22T01:17:13ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382020-09-011910.1177/1533033820945801MiR-331-3p Links to Drug Resistance of Pancreatic Cancer Cells by Activating WNT/β-Catenin Signal via ST7LTing Zhan MM0Xiaoli Chen MM1Xia Tian MM2Zheng Han MM3Meng Liu PhD4Yanli Zou MM5Shasha Huang MM6Aifang Chen MM7Xueting Cheng MM8Junsheng Deng MM9Jie Tan MM10Xiaodong Huang PhD11 Department of Gastroenterology, Wuhan Third Hospital, , Wuhan, China Department of Gastroenterology, Wuhan Third Hospital, , Wuhan, China Department of Gastroenterology, Wuhan Third Hospital, , Wuhan, China Department of Gastroenterology, Wuhan Third Hospital, , Wuhan, China Department of Gastroenterology, Wuhan Third Hospital, , Wuhan, China Department of Gastroenterology, Wuhan Third Hospital, , Wuhan, China Department of Gastroenterology, Wuhan Third Hospital, , Wuhan, China Department of Gastroenterology, Wuhan Third Hospital, , Wuhan, China Department of Gastroenterology, , Wuhan, China Department of Gastroenterology, , Wuhan, China Department of Gastroenterology, Wuhan Third Hospital, , Wuhan, China Department of Gastroenterology, Wuhan Third Hospital, , Wuhan, ChinaBackground: Pancreatic cancer is an aggressive type of cancer with poor prognosis, short survival rate, and high mortality. Drug resistance is a major cause of treatment failure in the disease. MiR-331-3p has been reported to play an important role in several cancers. We previously showed that miR-331-3p is upregulated in pancreatic cancer and promotes pancreatic cancer cell proliferation and epithelial-to-mesenchymal transition–mediated metastasis by targeting ST7L. However, it is uncertain whether miR-331-3p is involved in drug resistance. Methods: We investigated the relationship between miR-331-3p and pancreatic cancer drug resistance. As part of this, microRNA mimics or inhibitors were transfected into pancreatic cancer cells. Quantitative polymerase chain reaction was used to detect miR-331-3p expression, and flow cytometry was used to detect cell apoptosis. The Cell Counting Kit-8 assay was used to measure the IC50 values of gemcitabine in pancreatic cancer cells. The expression of multidrug resistance protein 1, multidrug resistance-related protein 1, breast cancer resistance protein, β-Catenin, c-Myc, Cyclin D1, Bcl-2, and Caspase-3 was evaluated by Western blotting. Results: We confirmed that miR-331-3p is upregulated in gemcitabine-treated pancreatic cancer cells and plasma from chemotherapy patients. We also confirmed that miR-331-3p inhibition decreased drug resistance by regulating cell apoptosis and multidrug resistance protein 1, multidrug resistance-related protein 1, and breast cancer resistance protein expression in pancreatic cancer cells, whereas miR-331-3p overexpression had the opposite effect. We further demonstrated that miR-331-3p effects in drug resistance were partially reversed by ST7L overexpression. In addition, overexpression of miR-331-3p activated Wnt/β-catenin signaling in pancreatic cancer cells, and ST7L overexpression restored activation of Wnt/β-catenin signaling. Conclusions: Taken together, our data demonstrate that miR-331-3p contributes to drug resistance by activating Wnt/β-catenin signaling via ST7L in pancreatic cancer cells. These data provide a theoretical basis for new targeted therapies in the future.https://doi.org/10.1177/1533033820945801 |
spellingShingle | Ting Zhan MM Xiaoli Chen MM Xia Tian MM Zheng Han MM Meng Liu PhD Yanli Zou MM Shasha Huang MM Aifang Chen MM Xueting Cheng MM Junsheng Deng MM Jie Tan MM Xiaodong Huang PhD MiR-331-3p Links to Drug Resistance of Pancreatic Cancer Cells by Activating WNT/β-Catenin Signal via ST7L Technology in Cancer Research & Treatment |
title | MiR-331-3p Links to Drug Resistance of Pancreatic Cancer Cells by Activating WNT/β-Catenin Signal via ST7L |
title_full | MiR-331-3p Links to Drug Resistance of Pancreatic Cancer Cells by Activating WNT/β-Catenin Signal via ST7L |
title_fullStr | MiR-331-3p Links to Drug Resistance of Pancreatic Cancer Cells by Activating WNT/β-Catenin Signal via ST7L |
title_full_unstemmed | MiR-331-3p Links to Drug Resistance of Pancreatic Cancer Cells by Activating WNT/β-Catenin Signal via ST7L |
title_short | MiR-331-3p Links to Drug Resistance of Pancreatic Cancer Cells by Activating WNT/β-Catenin Signal via ST7L |
title_sort | mir 331 3p links to drug resistance of pancreatic cancer cells by activating wnt β catenin signal via st7l |
url | https://doi.org/10.1177/1533033820945801 |
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