Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer

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Abstract

Background: RNA-binding proteins have an important role in messenger RNA (mRNA) regulation during tumour development and carcinogenesis. In the present study, we examined the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; hereafter refered to as IMPs) and Lin28 family expressions in epithelial ovarian carcinoma (EOC) patients and correlated their expression levels with the response to chemotherapy, hCTR1 expression and patient survival.Methods: Patients clinical information, real-time RT-PCR, immunohistochemistry, western blot, Transwell migration invasion assays, and cytotoxicity assays were used.Results: From 140 EOC patients, high expression of IMP3 or Lin28B was associated with poor survival, and women diagnosed at advanced stages with elevated IMP3 and Lin28B were at higher risk of developing chemoresistance. High IMP3 levels combined with high Lin28B levels significantly correlated with the poorest 5-year survival rates. Knockdown of IMP3 or Lin28B decreased cell proliferation, migration, and invasion, and increased the platinum sensitivity, but not taxol sensitivity, of ovarian cancer cells through increased expression of hCTR1, a copper transporter involved in platinum uptake. High expression of hCTR1 correlated with low expression of IMP3/Lin28B and better progression-free survival in advanced-stage EOC patients.Conclusion: Testing for a combination of elevated IMP3 and Lin28B levels could further facilitate the identification of a patient subgroup with the worst prognosis.

Original languageEnglish
Pages (from-to)414-424
Number of pages11
JournalBritish Journal of Cancer
Volume113
Issue number3
DOIs
Publication statusPublished - 2015 Jul 28

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RNA-Binding Proteins
Ovarian Neoplasms
Platinum
Carcinoma
Inosine Monophosphate
Messenger RNA
Survival
Somatomedins
Paclitaxel
Disease-Free Survival
Cell Movement
Real-Time Polymerase Chain Reaction
Copper
Carcinogenesis
Survival Rate
Western Blotting
Immunohistochemistry
Cell Proliferation
Drug Therapy
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{9a3085dc1ccb4fcf9be76d29b33244e9,
title = "Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer",
abstract = "Background: RNA-binding proteins have an important role in messenger RNA (mRNA) regulation during tumour development and carcinogenesis. In the present study, we examined the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; hereafter refered to as IMPs) and Lin28 family expressions in epithelial ovarian carcinoma (EOC) patients and correlated their expression levels with the response to chemotherapy, hCTR1 expression and patient survival.Methods: Patients clinical information, real-time RT-PCR, immunohistochemistry, western blot, Transwell migration invasion assays, and cytotoxicity assays were used.Results: From 140 EOC patients, high expression of IMP3 or Lin28B was associated with poor survival, and women diagnosed at advanced stages with elevated IMP3 and Lin28B were at higher risk of developing chemoresistance. High IMP3 levels combined with high Lin28B levels significantly correlated with the poorest 5-year survival rates. Knockdown of IMP3 or Lin28B decreased cell proliferation, migration, and invasion, and increased the platinum sensitivity, but not taxol sensitivity, of ovarian cancer cells through increased expression of hCTR1, a copper transporter involved in platinum uptake. High expression of hCTR1 correlated with low expression of IMP3/Lin28B and better progression-free survival in advanced-stage EOC patients.Conclusion: Testing for a combination of elevated IMP3 and Lin28B levels could further facilitate the identification of a patient subgroup with the worst prognosis.",
author = "Keng-Fu Hsu and Meng-Ru Shen and Yu-Fang Huang and Ya-Min Cheng and Sheng-Hsiang Lin and Nan-Haw Chow and Cheng, {S. W.} and Cheng-Yang Chou and Chung-Liang Ho",
year = "2015",
month = "7",
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doi = "10.1038/bjc.2015.254",
language = "English",
volume = "113",
pages = "414--424",
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T1 - Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer

AU - Hsu, Keng-Fu

AU - Shen, Meng-Ru

AU - Huang, Yu-Fang

AU - Cheng, Ya-Min

AU - Lin, Sheng-Hsiang

AU - Chow, Nan-Haw

AU - Cheng, S. W.

AU - Chou, Cheng-Yang

AU - Ho, Chung-Liang

PY - 2015/7/28

Y1 - 2015/7/28

N2 - Background: RNA-binding proteins have an important role in messenger RNA (mRNA) regulation during tumour development and carcinogenesis. In the present study, we examined the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; hereafter refered to as IMPs) and Lin28 family expressions in epithelial ovarian carcinoma (EOC) patients and correlated their expression levels with the response to chemotherapy, hCTR1 expression and patient survival.Methods: Patients clinical information, real-time RT-PCR, immunohistochemistry, western blot, Transwell migration invasion assays, and cytotoxicity assays were used.Results: From 140 EOC patients, high expression of IMP3 or Lin28B was associated with poor survival, and women diagnosed at advanced stages with elevated IMP3 and Lin28B were at higher risk of developing chemoresistance. High IMP3 levels combined with high Lin28B levels significantly correlated with the poorest 5-year survival rates. Knockdown of IMP3 or Lin28B decreased cell proliferation, migration, and invasion, and increased the platinum sensitivity, but not taxol sensitivity, of ovarian cancer cells through increased expression of hCTR1, a copper transporter involved in platinum uptake. High expression of hCTR1 correlated with low expression of IMP3/Lin28B and better progression-free survival in advanced-stage EOC patients.Conclusion: Testing for a combination of elevated IMP3 and Lin28B levels could further facilitate the identification of a patient subgroup with the worst prognosis.

AB - Background: RNA-binding proteins have an important role in messenger RNA (mRNA) regulation during tumour development and carcinogenesis. In the present study, we examined the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; hereafter refered to as IMPs) and Lin28 family expressions in epithelial ovarian carcinoma (EOC) patients and correlated their expression levels with the response to chemotherapy, hCTR1 expression and patient survival.Methods: Patients clinical information, real-time RT-PCR, immunohistochemistry, western blot, Transwell migration invasion assays, and cytotoxicity assays were used.Results: From 140 EOC patients, high expression of IMP3 or Lin28B was associated with poor survival, and women diagnosed at advanced stages with elevated IMP3 and Lin28B were at higher risk of developing chemoresistance. High IMP3 levels combined with high Lin28B levels significantly correlated with the poorest 5-year survival rates. Knockdown of IMP3 or Lin28B decreased cell proliferation, migration, and invasion, and increased the platinum sensitivity, but not taxol sensitivity, of ovarian cancer cells through increased expression of hCTR1, a copper transporter involved in platinum uptake. High expression of hCTR1 correlated with low expression of IMP3/Lin28B and better progression-free survival in advanced-stage EOC patients.Conclusion: Testing for a combination of elevated IMP3 and Lin28B levels could further facilitate the identification of a patient subgroup with the worst prognosis.

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