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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: SAGE Publishing 2020-09-01
Series:Technology in Cancer Research & Treatment
Online Access:https://doi.org/10.1177/1533033820945801
_version_ 1818527799356424192
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
format Article
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
publisher SAGE Publishing
record_format Article
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
work_keys_str_mv AT tingzhanmm mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT xiaolichenmm mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT xiatianmm mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT zhenghanmm mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT mengliuphd mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT yanlizoumm mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT shashahuangmm mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT aifangchenmm mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT xuetingchengmm mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT junshengdengmm mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT jietanmm mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l
AT xiaodonghuangphd mir3313plinkstodrugresistanceofpancreaticcancercellsbyactivatingwntbcateninsignalviast7l