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Title: H19 mediates methotrexate resistance in colorectal cancer through activating Wnt/β-catenin pathway

Abstract

Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. As one of the earliest cytotoxic drugs, methotrexate (MTX) serves as an anti-metabolite and anti-folate chemotherapy for various cancers. Unfortunately, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the therapeutic efficacy of MTX in clinics. Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years. More and more emerging evidences have demonstrated that they play important regulatory roles in various biological activities and disease progression including drug resistance. In the present study, a MTX-resistant colorectal cell line HT-29 (HT-29-R) was developed, which displayed the active proliferation and shortened cell cycle. LncRNA H19 was found to be significantly upregulated in this resistant cell line. Further investigation showed that H19 knockdown sensitized the MTX resistance in HT-29-R cells while its overexpression improved the MTX resistance in the parental cells, suggesting that H19 mediate MTX resistance. The Wnt/β-catenin signaling was activated in HT-29-R cells, and H19 knockdown suppressed this signaling in the parental cells. In conclusion, H19 mediated MTX resistance via activating Wnt/β-catenin signaling, which help to develop H19 as a promising therapeutic target for MTXmore » resistant CRC. - Highlights: • A methotrexate (MTX) -resistant colorectal cancer cell line HT-29 (HT-29-R) has been developed. • H19 was upregulated in HT-29-R cells. • H19 mediated MTX resistance in colorectal cancer (CRC). • Wnt/β-catenin pathway was involved in the H19-mediated MTX resistance in CRC cells.« less

Authors:
 [1];  [2];  [3];  [4];  [2];  [3];  [4]
  1. Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong (China)
  2. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China)
  3. Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (China)
  4. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 (China)
Publication Date:
OSTI Identifier:
22649813
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 350; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BROMIDES; CELL CYCLE; CELL PROLIFERATION; CHEMOTHERAPY; IODIDES; METABOLITES; METHOTREXATE; NEOPLASMS; OXIDOREDUCTASES; RNA

Citation Formats

Wu, Ke-feng, Liang, Wei-Cheng, Feng, Lu, Pang, Jian-xin, Waye, Mary Miu-Yee, Zhang, Jin-Fang, and Fu, Wei-Ming, E-mail: fuweiming76@smu.edu.cn. H19 mediates methotrexate resistance in colorectal cancer through activating Wnt/β-catenin pathway. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2016.12.003.
Wu, Ke-feng, Liang, Wei-Cheng, Feng, Lu, Pang, Jian-xin, Waye, Mary Miu-Yee, Zhang, Jin-Fang, & Fu, Wei-Ming, E-mail: fuweiming76@smu.edu.cn. H19 mediates methotrexate resistance in colorectal cancer through activating Wnt/β-catenin pathway. United States. doi:10.1016/J.YEXCR.2016.12.003.
Wu, Ke-feng, Liang, Wei-Cheng, Feng, Lu, Pang, Jian-xin, Waye, Mary Miu-Yee, Zhang, Jin-Fang, and Fu, Wei-Ming, E-mail: fuweiming76@smu.edu.cn. Sun . "H19 mediates methotrexate resistance in colorectal cancer through activating Wnt/β-catenin pathway". United States. doi:10.1016/J.YEXCR.2016.12.003.
@article{osti_22649813,
title = {H19 mediates methotrexate resistance in colorectal cancer through activating Wnt/β-catenin pathway},
author = {Wu, Ke-feng and Liang, Wei-Cheng and Feng, Lu and Pang, Jian-xin and Waye, Mary Miu-Yee and Zhang, Jin-Fang and Fu, Wei-Ming, E-mail: fuweiming76@smu.edu.cn},
abstractNote = {Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. As one of the earliest cytotoxic drugs, methotrexate (MTX) serves as an anti-metabolite and anti-folate chemotherapy for various cancers. Unfortunately, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the therapeutic efficacy of MTX in clinics. Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years. More and more emerging evidences have demonstrated that they play important regulatory roles in various biological activities and disease progression including drug resistance. In the present study, a MTX-resistant colorectal cell line HT-29 (HT-29-R) was developed, which displayed the active proliferation and shortened cell cycle. LncRNA H19 was found to be significantly upregulated in this resistant cell line. Further investigation showed that H19 knockdown sensitized the MTX resistance in HT-29-R cells while its overexpression improved the MTX resistance in the parental cells, suggesting that H19 mediate MTX resistance. The Wnt/β-catenin signaling was activated in HT-29-R cells, and H19 knockdown suppressed this signaling in the parental cells. In conclusion, H19 mediated MTX resistance via activating Wnt/β-catenin signaling, which help to develop H19 as a promising therapeutic target for MTX resistant CRC. - Highlights: • A methotrexate (MTX) -resistant colorectal cancer cell line HT-29 (HT-29-R) has been developed. • H19 was upregulated in HT-29-R cells. • H19 mediated MTX resistance in colorectal cancer (CRC). • Wnt/β-catenin pathway was involved in the H19-mediated MTX resistance in CRC cells.},
doi = {10.1016/J.YEXCR.2016.12.003},
journal = {Experimental Cell Research},
number = 2,
volume = 350,
place = {United States},
year = {Sun Jan 15 00:00:00 EST 2017},
month = {Sun Jan 15 00:00:00 EST 2017}
}