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miR-1290 Is a Biomarker in DNA-Mismatch-Repair-Deficient Colon Cancer and Promotes Resistance to 5-Fluorouracil by Directly Targeting hMSH2
5-Fluorouracil (5FU)-based adjuvant therapy is the first-line therapy for treating stage II and III colon cancer after surgery. However, its therapeutic efficacy is limited because of chemoresistance, especially in deficient mismatch repair (dMMR) colon cancer. Here, we first used laser capture micr...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society of Gene & Cell Therapy
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443909/ https://www.ncbi.nlm.nih.gov/pubmed/28624221 http://dx.doi.org/10.1016/j.omtn.2017.05.006 |
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author | Ye, Ling Jiang, Tao Shao, Huanzhang Zhong, Lin Wang, Zhaowen Liu, Yuan Tang, Huamei Qin, Bingyu Zhang, Xiaoqing Fan, Junwei |
author_facet | Ye, Ling Jiang, Tao Shao, Huanzhang Zhong, Lin Wang, Zhaowen Liu, Yuan Tang, Huamei Qin, Bingyu Zhang, Xiaoqing Fan, Junwei |
author_sort | Ye, Ling |
collection | PubMed |
description | 5-Fluorouracil (5FU)-based adjuvant therapy is the first-line therapy for treating stage II and III colon cancer after surgery. However, its therapeutic efficacy is limited because of chemoresistance, especially in deficient mismatch repair (dMMR) colon cancer. Here, we first used laser capture microdissection to obtain purified cells from four dMMR and four proficient mismatch repair (pMMR) colon cancer tissues. Second, microRNA (miRNA) microarray chips were used to identify miRNAs that are differentially expressed between these two classes of tumors. Third, we analyzed their differential expression by qRT-PCR in a panel of 5-FU-resistant colon cancer cell lines. We identified that miR-1290 was one of the most upregulated miRNAs in both dMMR colon cancer tissues and 5-FU-resistant cells. We also found that miR-1290 was positively correlated with dMMR status and predicted poor prognosis in stage II and III colon cancer patients who received 5-FU-based chemotherapy. Furthermore, we demonstrated that inhibition of the expression of miR-1290 enhanced sensitivity to 5-FU treatment in vitro and in tumor xenografts in vivo by direct targeting hMSH2. Our study indicates that miR-1290 may become a promising biomarker of dMMR colon cancer and predicts the prognosis of stage II and III patients who receive 5-FU-based adjuvant therapy. |
format | Online Article Text |
id | pubmed-5443909 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-54439092017-06-01 miR-1290 Is a Biomarker in DNA-Mismatch-Repair-Deficient Colon Cancer and Promotes Resistance to 5-Fluorouracil by Directly Targeting hMSH2 Ye, Ling Jiang, Tao Shao, Huanzhang Zhong, Lin Wang, Zhaowen Liu, Yuan Tang, Huamei Qin, Bingyu Zhang, Xiaoqing Fan, Junwei Mol Ther Nucleic Acids Original Article 5-Fluorouracil (5FU)-based adjuvant therapy is the first-line therapy for treating stage II and III colon cancer after surgery. However, its therapeutic efficacy is limited because of chemoresistance, especially in deficient mismatch repair (dMMR) colon cancer. Here, we first used laser capture microdissection to obtain purified cells from four dMMR and four proficient mismatch repair (pMMR) colon cancer tissues. Second, microRNA (miRNA) microarray chips were used to identify miRNAs that are differentially expressed between these two classes of tumors. Third, we analyzed their differential expression by qRT-PCR in a panel of 5-FU-resistant colon cancer cell lines. We identified that miR-1290 was one of the most upregulated miRNAs in both dMMR colon cancer tissues and 5-FU-resistant cells. We also found that miR-1290 was positively correlated with dMMR status and predicted poor prognosis in stage II and III colon cancer patients who received 5-FU-based chemotherapy. Furthermore, we demonstrated that inhibition of the expression of miR-1290 enhanced sensitivity to 5-FU treatment in vitro and in tumor xenografts in vivo by direct targeting hMSH2. Our study indicates that miR-1290 may become a promising biomarker of dMMR colon cancer and predicts the prognosis of stage II and III patients who receive 5-FU-based adjuvant therapy. American Society of Gene & Cell Therapy 2017-05-12 /pmc/articles/PMC5443909/ /pubmed/28624221 http://dx.doi.org/10.1016/j.omtn.2017.05.006 Text en © 2017 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 | Original Article Ye, Ling Jiang, Tao Shao, Huanzhang Zhong, Lin Wang, Zhaowen Liu, Yuan Tang, Huamei Qin, Bingyu Zhang, Xiaoqing Fan, Junwei miR-1290 Is a Biomarker in DNA-Mismatch-Repair-Deficient Colon Cancer and Promotes Resistance to 5-Fluorouracil by Directly Targeting hMSH2 |
title | miR-1290 Is a Biomarker in DNA-Mismatch-Repair-Deficient Colon Cancer and Promotes Resistance to 5-Fluorouracil by Directly Targeting hMSH2 |
title_full | miR-1290 Is a Biomarker in DNA-Mismatch-Repair-Deficient Colon Cancer and Promotes Resistance to 5-Fluorouracil by Directly Targeting hMSH2 |
title_fullStr | miR-1290 Is a Biomarker in DNA-Mismatch-Repair-Deficient Colon Cancer and Promotes Resistance to 5-Fluorouracil by Directly Targeting hMSH2 |
title_full_unstemmed | miR-1290 Is a Biomarker in DNA-Mismatch-Repair-Deficient Colon Cancer and Promotes Resistance to 5-Fluorouracil by Directly Targeting hMSH2 |
title_short | miR-1290 Is a Biomarker in DNA-Mismatch-Repair-Deficient Colon Cancer and Promotes Resistance to 5-Fluorouracil by Directly Targeting hMSH2 |
title_sort | mir-1290 is a biomarker in dna-mismatch-repair-deficient colon cancer and promotes resistance to 5-fluorouracil by directly targeting hmsh2 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443909/ https://www.ncbi.nlm.nih.gov/pubmed/28624221 http://dx.doi.org/10.1016/j.omtn.2017.05.006 |
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