LIM-Domain-Binding Protein 1 Mediates Cell Proliferation and Drug Resistance in Colorectal Cancer

Objective: It has been shown that LIM-domain-binding protein 1 (LDB1) is involved in the tumorigenesis of several cancers, but its function in colorectal cancer (CRC) has not been fully explained. This study is aimed to investigate whether LDB1 is involved in regulating the cell growth and drug sens...

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Main Authors: Mo Zhu, Baofei Jiang, Hao Zuo, Xiaopeng Wang, Hengfa Ge, Ziming Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Surgery
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fsurg.2021.790380/full
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author Mo Zhu
Baofei Jiang
Hao Zuo
Xiaopeng Wang
Hengfa Ge
Ziming Huang
author_facet Mo Zhu
Baofei Jiang
Hao Zuo
Xiaopeng Wang
Hengfa Ge
Ziming Huang
author_sort Mo Zhu
collection DOAJ
description Objective: It has been shown that LIM-domain-binding protein 1 (LDB1) is involved in the tumorigenesis of several cancers, but its function in colorectal cancer (CRC) has not been fully explained. This study is aimed to investigate whether LDB1 is involved in regulating the cell growth and drug sensitivity of CRC.Methods: To analyze the protein expression of LDB1 in CRC tissues, western blot was used. KM plotter and UALCAN databases were used to predict the prognosis of CRC patients with low or high LDB1 expression. To do the correlation analysis in CRC tissues, GEPIA database was used. CCK-8 assay and xenograft models were used to evaluate the effects of LDB1 in CRC cell growth. An oxaliplatin-resistant cell line was constructed to evaluate the effect of LDB1 in drug sensitivity of CRC cells.Results: Our current research confirmed that LDB1 was upregulated in CRC tumor tissues, and its elevation predicted a poor prognosis for CRC patients. LDB1 was also found positively correlated with CCNA1, BCL2 and BCLW, but negatively correlated with the pro-apoptotic signals (BID, BAX and BAK). Silence of LDB1 significantly inhibited CRC cell growth in vitro, and CRC cells with low expression of LDB1 had a lower tumorigenesis rate in tumor-bearing nude mice. Our experiments also showed that LDB1 silence enhanced the anti-tumor activity of oxaliplatin in CRC cells. The expression of LDB1 was also found increased in oxaliplatin-resistant CRC cell lines, and silence of LDB1 partly restored the antitumor effect of oxaliplatin in an oxaliplatin-resistant CRC cell line.Conclusion: Our current results revealed the roles of LDB1 in the growth and drug resistance of CRC cells, and may provide the new theoretical support for LDB1 as a potential target for the treatment of CRC in the future.
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spelling doaj.art-17053a73adb4480096ba7be0b4539b692022-12-22T04:03:42ZengFrontiers Media S.A.Frontiers in Surgery2296-875X2022-01-01810.3389/fsurg.2021.790380790380LIM-Domain-Binding Protein 1 Mediates Cell Proliferation and Drug Resistance in Colorectal CancerMo Zhu0Baofei Jiang1Hao Zuo2Xiaopeng Wang3Hengfa Ge4Ziming Huang5Department of Gastrointestinal Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, ChinaDepartment of Gastrointestinal Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, ChinaDepartment of Gastrointestinal Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, ChinaDepartment of Gastrointestinal Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, ChinaDepartment of Emergency Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, ChinaDepartment of Emergency Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, ChinaObjective: It has been shown that LIM-domain-binding protein 1 (LDB1) is involved in the tumorigenesis of several cancers, but its function in colorectal cancer (CRC) has not been fully explained. This study is aimed to investigate whether LDB1 is involved in regulating the cell growth and drug sensitivity of CRC.Methods: To analyze the protein expression of LDB1 in CRC tissues, western blot was used. KM plotter and UALCAN databases were used to predict the prognosis of CRC patients with low or high LDB1 expression. To do the correlation analysis in CRC tissues, GEPIA database was used. CCK-8 assay and xenograft models were used to evaluate the effects of LDB1 in CRC cell growth. An oxaliplatin-resistant cell line was constructed to evaluate the effect of LDB1 in drug sensitivity of CRC cells.Results: Our current research confirmed that LDB1 was upregulated in CRC tumor tissues, and its elevation predicted a poor prognosis for CRC patients. LDB1 was also found positively correlated with CCNA1, BCL2 and BCLW, but negatively correlated with the pro-apoptotic signals (BID, BAX and BAK). Silence of LDB1 significantly inhibited CRC cell growth in vitro, and CRC cells with low expression of LDB1 had a lower tumorigenesis rate in tumor-bearing nude mice. Our experiments also showed that LDB1 silence enhanced the anti-tumor activity of oxaliplatin in CRC cells. The expression of LDB1 was also found increased in oxaliplatin-resistant CRC cell lines, and silence of LDB1 partly restored the antitumor effect of oxaliplatin in an oxaliplatin-resistant CRC cell line.Conclusion: Our current results revealed the roles of LDB1 in the growth and drug resistance of CRC cells, and may provide the new theoretical support for LDB1 as a potential target for the treatment of CRC in the future.https://www.frontiersin.org/articles/10.3389/fsurg.2021.790380/fullLIM-domain-binding protein 1cell growthdrug sensitivityoxaliplatincolorectal cancer
spellingShingle Mo Zhu
Baofei Jiang
Hao Zuo
Xiaopeng Wang
Hengfa Ge
Ziming Huang
LIM-Domain-Binding Protein 1 Mediates Cell Proliferation and Drug Resistance in Colorectal Cancer
Frontiers in Surgery
LIM-domain-binding protein 1
cell growth
drug sensitivity
oxaliplatin
colorectal cancer
title LIM-Domain-Binding Protein 1 Mediates Cell Proliferation and Drug Resistance in Colorectal Cancer
title_full LIM-Domain-Binding Protein 1 Mediates Cell Proliferation and Drug Resistance in Colorectal Cancer
title_fullStr LIM-Domain-Binding Protein 1 Mediates Cell Proliferation and Drug Resistance in Colorectal Cancer
title_full_unstemmed LIM-Domain-Binding Protein 1 Mediates Cell Proliferation and Drug Resistance in Colorectal Cancer
title_short LIM-Domain-Binding Protein 1 Mediates Cell Proliferation and Drug Resistance in Colorectal Cancer
title_sort lim domain binding protein 1 mediates cell proliferation and drug resistance in colorectal cancer
topic LIM-domain-binding protein 1
cell growth
drug sensitivity
oxaliplatin
colorectal cancer
url https://www.frontiersin.org/articles/10.3389/fsurg.2021.790380/full
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