Clinical implications of aldo-keto reductase family 1 member C3 and its relationship with lipocalin 2 in cancer of the uterine cervix

Chih Hsien Wu, Jiunn Liang Ko, Shiuan Chih Chen, Yu Wen Lin, Chih Ping Han, Ti Yuan Yang, Ming Hsien Chien, Po Hui Wang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objective Over-expression of the aldo-keto reductase family 1 member C3 (AKR1C3) has been demonstrated in many human cancers. Lipocalin 2 (LCN2) is reported to inhibit cervical cancer metastasis but little is known regarding its relationship with AKR1C3 in the development and progression of uterine cervical cancer. This study aimed to investigate the involvement of AKR1C3 and its relationship with LCN2 in cervical cancer. Methods The roles of AKR1C3 and LCN2 were investigated using the lentivirus shRNA system in SiHa and Caski cervical cancer cells. LCN2 and matrix metalloproteinase-2 (MMP-2) promoters were constructed to demonstrate transcriptional regulation by shAKR1C3 and shLCN2, respectively. The influences of metastatic phenotypes were analyzed by wound healing, Boyden chamber, and immunofluorescence assays. The activity of MMP-2 was determined by zymography assay. The impacts of AKR1C3 and LCN2 on patient prognosis were evaluated using tissue microarrays by Cox regression and Kaplan-Meier models. Results Silencing of the AKR1C3 gene increased the expression of LCN2 and decreased the migratory and invasive abilities and changed the cytoskeleton of cervical cancer cells. When AKR1C3 was over-expressed, it decreased LCN2 promoter activity and LCN2 expression and increased cell migration. The mRNA level and enzyme activity of MMP-2 increased in silenced LCN2 cells. Positive AKR1C3 and negative LCN2 were correlated with higher recurrence and poorer survival of cervical cancer patients. Conclusions Silencing of AKR1C3 increases LCN2 expression and inhibits metastasis in cervical cancer. Both AKR1C3 and LCN2 serve as molecular targets for cancer therapy to improve the clinical outcome of cervical cancer patients.

Original languageEnglish
Pages (from-to)474-482
Number of pages9
JournalGynecologic Oncology
Volume132
Issue number2
DOIs
Publication statusPublished - Feb 2014

Fingerprint

Uterine Cervical Neoplasms
Matrix Metalloproteinase 2
Lipocalin-2
carbonyl reductase (NADPH)
Neoplasm Metastasis
Lentivirus
Aptitude
Cytoskeleton
Wound Healing
Small Interfering RNA
Cell Movement
Fluorescent Antibody Technique
Neoplasms
Phenotype
Gene Expression
Recurrence
Messenger RNA
Survival

Keywords

  • Aldo-keto reductase family 1 member C3
  • Cancer of the uterine cervix
  • Lipocalin 2
  • Matrix metalloproteinase-2
  • Metastasis

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

Clinical implications of aldo-keto reductase family 1 member C3 and its relationship with lipocalin 2 in cancer of the uterine cervix. / Wu, Chih Hsien; Ko, Jiunn Liang; Chen, Shiuan Chih; Lin, Yu Wen; Han, Chih Ping; Yang, Ti Yuan; Chien, Ming Hsien; Wang, Po Hui.

In: Gynecologic Oncology, Vol. 132, No. 2, 02.2014, p. 474-482.

Research output: Contribution to journalArticle

Wu, Chih Hsien ; Ko, Jiunn Liang ; Chen, Shiuan Chih ; Lin, Yu Wen ; Han, Chih Ping ; Yang, Ti Yuan ; Chien, Ming Hsien ; Wang, Po Hui. / Clinical implications of aldo-keto reductase family 1 member C3 and its relationship with lipocalin 2 in cancer of the uterine cervix. In: Gynecologic Oncology. 2014 ; Vol. 132, No. 2. pp. 474-482.
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abstract = "Objective Over-expression of the aldo-keto reductase family 1 member C3 (AKR1C3) has been demonstrated in many human cancers. Lipocalin 2 (LCN2) is reported to inhibit cervical cancer metastasis but little is known regarding its relationship with AKR1C3 in the development and progression of uterine cervical cancer. This study aimed to investigate the involvement of AKR1C3 and its relationship with LCN2 in cervical cancer. Methods The roles of AKR1C3 and LCN2 were investigated using the lentivirus shRNA system in SiHa and Caski cervical cancer cells. LCN2 and matrix metalloproteinase-2 (MMP-2) promoters were constructed to demonstrate transcriptional regulation by shAKR1C3 and shLCN2, respectively. The influences of metastatic phenotypes were analyzed by wound healing, Boyden chamber, and immunofluorescence assays. The activity of MMP-2 was determined by zymography assay. The impacts of AKR1C3 and LCN2 on patient prognosis were evaluated using tissue microarrays by Cox regression and Kaplan-Meier models. Results Silencing of the AKR1C3 gene increased the expression of LCN2 and decreased the migratory and invasive abilities and changed the cytoskeleton of cervical cancer cells. When AKR1C3 was over-expressed, it decreased LCN2 promoter activity and LCN2 expression and increased cell migration. The mRNA level and enzyme activity of MMP-2 increased in silenced LCN2 cells. Positive AKR1C3 and negative LCN2 were correlated with higher recurrence and poorer survival of cervical cancer patients. Conclusions Silencing of AKR1C3 increases LCN2 expression and inhibits metastasis in cervical cancer. Both AKR1C3 and LCN2 serve as molecular targets for cancer therapy to improve the clinical outcome of cervical cancer patients.",
keywords = "Aldo-keto reductase family 1 member C3, Cancer of the uterine cervix, Lipocalin 2, Matrix metalloproteinase-2, Metastasis",
author = "Wu, {Chih Hsien} and Ko, {Jiunn Liang} and Chen, {Shiuan Chih} and Lin, {Yu Wen} and Han, {Chih Ping} and Yang, {Ti Yuan} and Chien, {Ming Hsien} and Wang, {Po Hui}",
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T1 - Clinical implications of aldo-keto reductase family 1 member C3 and its relationship with lipocalin 2 in cancer of the uterine cervix

AU - Wu, Chih Hsien

AU - Ko, Jiunn Liang

AU - Chen, Shiuan Chih

AU - Lin, Yu Wen

AU - Han, Chih Ping

AU - Yang, Ti Yuan

AU - Chien, Ming Hsien

AU - Wang, Po Hui

PY - 2014/2

Y1 - 2014/2

N2 - Objective Over-expression of the aldo-keto reductase family 1 member C3 (AKR1C3) has been demonstrated in many human cancers. Lipocalin 2 (LCN2) is reported to inhibit cervical cancer metastasis but little is known regarding its relationship with AKR1C3 in the development and progression of uterine cervical cancer. This study aimed to investigate the involvement of AKR1C3 and its relationship with LCN2 in cervical cancer. Methods The roles of AKR1C3 and LCN2 were investigated using the lentivirus shRNA system in SiHa and Caski cervical cancer cells. LCN2 and matrix metalloproteinase-2 (MMP-2) promoters were constructed to demonstrate transcriptional regulation by shAKR1C3 and shLCN2, respectively. The influences of metastatic phenotypes were analyzed by wound healing, Boyden chamber, and immunofluorescence assays. The activity of MMP-2 was determined by zymography assay. The impacts of AKR1C3 and LCN2 on patient prognosis were evaluated using tissue microarrays by Cox regression and Kaplan-Meier models. Results Silencing of the AKR1C3 gene increased the expression of LCN2 and decreased the migratory and invasive abilities and changed the cytoskeleton of cervical cancer cells. When AKR1C3 was over-expressed, it decreased LCN2 promoter activity and LCN2 expression and increased cell migration. The mRNA level and enzyme activity of MMP-2 increased in silenced LCN2 cells. Positive AKR1C3 and negative LCN2 were correlated with higher recurrence and poorer survival of cervical cancer patients. Conclusions Silencing of AKR1C3 increases LCN2 expression and inhibits metastasis in cervical cancer. Both AKR1C3 and LCN2 serve as molecular targets for cancer therapy to improve the clinical outcome of cervical cancer patients.

AB - Objective Over-expression of the aldo-keto reductase family 1 member C3 (AKR1C3) has been demonstrated in many human cancers. Lipocalin 2 (LCN2) is reported to inhibit cervical cancer metastasis but little is known regarding its relationship with AKR1C3 in the development and progression of uterine cervical cancer. This study aimed to investigate the involvement of AKR1C3 and its relationship with LCN2 in cervical cancer. Methods The roles of AKR1C3 and LCN2 were investigated using the lentivirus shRNA system in SiHa and Caski cervical cancer cells. LCN2 and matrix metalloproteinase-2 (MMP-2) promoters were constructed to demonstrate transcriptional regulation by shAKR1C3 and shLCN2, respectively. The influences of metastatic phenotypes were analyzed by wound healing, Boyden chamber, and immunofluorescence assays. The activity of MMP-2 was determined by zymography assay. The impacts of AKR1C3 and LCN2 on patient prognosis were evaluated using tissue microarrays by Cox regression and Kaplan-Meier models. Results Silencing of the AKR1C3 gene increased the expression of LCN2 and decreased the migratory and invasive abilities and changed the cytoskeleton of cervical cancer cells. When AKR1C3 was over-expressed, it decreased LCN2 promoter activity and LCN2 expression and increased cell migration. The mRNA level and enzyme activity of MMP-2 increased in silenced LCN2 cells. Positive AKR1C3 and negative LCN2 were correlated with higher recurrence and poorer survival of cervical cancer patients. Conclusions Silencing of AKR1C3 increases LCN2 expression and inhibits metastasis in cervical cancer. Both AKR1C3 and LCN2 serve as molecular targets for cancer therapy to improve the clinical outcome of cervical cancer patients.

KW - Aldo-keto reductase family 1 member C3

KW - Cancer of the uterine cervix

KW - Lipocalin 2

KW - Matrix metalloproteinase-2

KW - Metastasis

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