Next Article in Journal
SERPINB2 Is a Novel Indicator of Cancer Stem Cell Tumorigenicity in Multiple Cancer Types
Previous Article in Journal
Head and Body/Tail Pancreatic Carcinomas Are Not the Same Tumors
Previous Article in Special Issue
ADRB2-Targeting Therapies for Prostate Cancer
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Cancers 2019, 11(4), 498; https://doi.org/10.3390/cancers11040498

Epsilon-Globin HBE1 Enhances Radiotherapy Resistance by Down-Regulating BCL11A in Colorectal Cancer Cells

1
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea
2
Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Korea
3
Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea
4
Department of Biomolecular Science, University of Science and Technology (UST), Daejeon 34141, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 12 February 2019 / Revised: 27 March 2019 / Accepted: 2 April 2019 / Published: 8 April 2019
(This article belongs to the Special Issue Apoptosis in Cancer)
  |  
PDF [6292 KB, uploaded 23 April 2019]
  |     |  

Abstract

Resistance to radiotherapy is considered an important obstacle in the treatment of colorectal cancer. However, the mechanisms that enable tumor cells to tolerate the effects of radiation remain unclear. Moreover, radiotherapy causes accumulated mutations in transcription factors, which can lead to changes in gene expression and radiosensitivity. This phenomenon reduces the effectiveness of radiation therapy towards cancer cells. In the present study, radiation-resistant (RR) cancer cells were established by sequential radiation exposure, and hemoglobin subunit epsilon 1 (HBE1) was identified as a candidate radiation resistance-associated protein based on RNA-sequencing analysis. Then, compared to radiosensitive (RS) cell lines, the overexpression of HBE1 in RR cell lines was used to measure various forms of radiation-induced cellular damage. Consequently, HBE1-overexpressing cell lines were found to exhibit decreased radiation-induced intracellular reactive oxygen species (ROS) production and cell mortality. Conversely, HBE1 deficiency in RR cell lines increased intracellular ROS production, G2/M arrest, and apoptosis, and decreased clonogenic survival rate. These effects were reversed by the ROS scavenger N-acetyl cysteine. Moreover, HBE1 overexpression was found to attenuate radiation-induced endoplasmic reticulum stress and apoptosis via an inositol-requiring enzyme 1(IRE1)—Jun amino-terminal kinase (JNK) signaling pathway. In addition, increased HBE1 expression induced by γ-irradiation in RS cells attenuated expression of the transcriptional regulator BCL11A, whereas its depletion in RR cells increased BCL11A expression. Collectively, these observations indicate that the expression of HBE1 during radiotherapy might potentiate the survival of radiation-exposed colorectal cancer cells. View Full-Text
Keywords: ER stress; HBE1; BCL11A; JNK; radioresistant; oxidative stress; cell cycle arrest ER stress; HBE1; BCL11A; JNK; radioresistant; oxidative stress; cell cycle arrest
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Park, S.Y.; Lee, S.-J.; Cho, H.J.; Kim, J.-T.; Yoon, H.R.; Lee, K.H.; Kim, B.Y.; Lee, Y.; Lee, H.G. Epsilon-Globin HBE1 Enhances Radiotherapy Resistance by Down-Regulating BCL11A in Colorectal Cancer Cells. Cancers 2019, 11, 498.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top