Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling
Abstract Colorectal cancer (CRC) is still the third most common cancer in the world with a limited prognosis due to the chemoresistance of CRC cells to 5‐fluorouracil (5‐FU)‐based chemotherapy. In our previous study, we revealed that miR‐204 overexpression could sensitize CRC cell to 5‐FU treatment...
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Wiley
2019-05-01
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Series: | Cancer Medicine |
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Online Access: | https://doi.org/10.1002/cam4.1809 |
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author | Haijun Wu Qiongyan Zou Hong He Yu Liang Mingjun Lei Qin Zhou Dan Fan Liangfang Shen |
author_facet | Haijun Wu Qiongyan Zou Hong He Yu Liang Mingjun Lei Qin Zhou Dan Fan Liangfang Shen |
author_sort | Haijun Wu |
collection | DOAJ |
description | Abstract Colorectal cancer (CRC) is still the third most common cancer in the world with a limited prognosis due to the chemoresistance of CRC cells to 5‐fluorouracil (5‐FU)‐based chemotherapy. In our previous study, we revealed that miR‐204 overexpression could sensitize CRC cell to 5‐FU treatment through targeting HMGA2/PI3K signaling pathway; however, miR‐204 expression in CRC tissues is abnormally downregulated. Long non‐coding RNAs (lncRNAs) dysregulation has been reported in human diseases, including cancer. Also, lncRNA can regulate cancer cell proliferation, invasion, migration, as well as chemoresistance. LncRNA prostate cancer‐associated transcript 6 (PCAT6) acts as an oncogene in many cancers; herein, PCAT6 expression was abnormally upregulated in CRC tissues and cell lines, suggesting its potential role in CRC. Further, we assessed the specific function and mechanism of PCAT6 in CRC. Furthermore, we revealed that PCAT6 knockdown attenuated CRC chemoresistance to 5‐FU through miR‐204/HMGA2/PI3K; miR‐204 inhibition could partially reverse the effect of PCAT6 knockdown. Taken together, we demonstrate that the abnormal PCAT6 overexpression inhibits miR‐204 expression in CRC, thereby promoting HMGA2/PI3K signaling activity, ultimately enhancing the chemoresistance of CRC cells to 5‐FU; PCAT6 represents a promising target for dealing with CRC chemoresistance. |
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issn | 2045-7634 |
language | English |
last_indexed | 2024-04-24T17:10:43Z |
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spelling | doaj.art-91fa34660aff4c5ab1f7d673ceca58a32024-03-28T10:30:36ZengWileyCancer Medicine2045-76342019-05-01852484249510.1002/cam4.1809Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signalingHaijun Wu0Qiongyan Zou1Hong He2Yu Liang3Mingjun Lei4Qin Zhou5Dan Fan6Liangfang Shen7Department of Oncology Xiangya Hospital, Central South University Changsha ChinaDepartment of Breast and Thyroid The Second Xiangya Hospital, Central South University Changsha ChinaDepartment of Medical Records Information The First Hospital of Changsha Changsha ChinaDepartment of Oncology Xiangya Hospital, Central South University Changsha ChinaDepartment of Oncology Xiangya Hospital, Central South University Changsha ChinaDepartment of Oncology Xiangya Hospital, Central South University Changsha ChinaDepartment of Oncology Xiangya Hospital, Central South University Changsha ChinaDepartment of Oncology Xiangya Hospital, Central South University Changsha ChinaAbstract Colorectal cancer (CRC) is still the third most common cancer in the world with a limited prognosis due to the chemoresistance of CRC cells to 5‐fluorouracil (5‐FU)‐based chemotherapy. In our previous study, we revealed that miR‐204 overexpression could sensitize CRC cell to 5‐FU treatment through targeting HMGA2/PI3K signaling pathway; however, miR‐204 expression in CRC tissues is abnormally downregulated. Long non‐coding RNAs (lncRNAs) dysregulation has been reported in human diseases, including cancer. Also, lncRNA can regulate cancer cell proliferation, invasion, migration, as well as chemoresistance. LncRNA prostate cancer‐associated transcript 6 (PCAT6) acts as an oncogene in many cancers; herein, PCAT6 expression was abnormally upregulated in CRC tissues and cell lines, suggesting its potential role in CRC. Further, we assessed the specific function and mechanism of PCAT6 in CRC. Furthermore, we revealed that PCAT6 knockdown attenuated CRC chemoresistance to 5‐FU through miR‐204/HMGA2/PI3K; miR‐204 inhibition could partially reverse the effect of PCAT6 knockdown. Taken together, we demonstrate that the abnormal PCAT6 overexpression inhibits miR‐204 expression in CRC, thereby promoting HMGA2/PI3K signaling activity, ultimately enhancing the chemoresistance of CRC cells to 5‐FU; PCAT6 represents a promising target for dealing with CRC chemoresistance.https://doi.org/10.1002/cam4.18095‐fluorouracilchemoresistancecolorectal cancerHMGA2lncRNA prostate cancer‐associated transcript 6miR‐204 |
spellingShingle | Haijun Wu Qiongyan Zou Hong He Yu Liang Mingjun Lei Qin Zhou Dan Fan Liangfang Shen Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling Cancer Medicine 5‐fluorouracil chemoresistance colorectal cancer HMGA2 lncRNA prostate cancer‐associated transcript 6 miR‐204 |
title | Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling |
title_full | Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling |
title_fullStr | Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling |
title_full_unstemmed | Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling |
title_short | Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling |
title_sort | long non coding rna pcat6 targets mir 204 to modulate the chemoresistance of colorectal cancer cells to 5 fluorouracil based treatment through hmga2 signaling |
topic | 5‐fluorouracil chemoresistance colorectal cancer HMGA2 lncRNA prostate cancer‐associated transcript 6 miR‐204 |
url | https://doi.org/10.1002/cam4.1809 |
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