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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Main Authors: Haijun Wu, Qiongyan Zou, Hong He, Yu Liang, Mingjun Lei, Qin Zhou, Dan Fan, Liangfang Shen
Format: Article
Language:English
Published: Wiley 2019-05-01
Series:Cancer Medicine
Subjects:
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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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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