NRG1 regulates redox homeostasis via NRF2 in papillary thyroid cancer

Ting Ting Zhang, Ning Qu, Guo Hua Sun, Long Zhang, Yu Wang, Yuan Jin Wang, Xiang Ming Mu, Wen Jun Wei, Yu Long Wang, Qing Hai Ji, Yong Xue Zhu, Rong Liang Shi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Thyroid cancer is a common endocrine cancer, of which papillary thyroid cancer (PTC) is the most common type. Neuregulin 1 (NRG1), a glycoprotein mediating cell-cell signaling, plays vital roles in cellular activities; however, its role in PTC progression remains poorly understood. In this study, we performed immunohistochemistry in 196 samples from patients and found that NRG1, a potential prognostic marker is highly expressed in PTC compared with adjacent normal tissues. Cell Counting kit-8 (CCK-8) and clone formation assays indicated that NRG1 is essential for PTC cell viability and proliferation, probably by regulating redox homeostasis, which was implied by ROS generation analysis and intracellular GSH activity assay. Western blot analysis and RT-qPCR revealed that NRG1 regulates ERK pathway and the pivotal regulator of cellular redox status, nuclear factor E2-related factor 2 (NRF2), which maintains moderate reactive oxygen species (ROS) levels through a set of antioxidant response element (ARE)-containing genes. The immunohistochemical scoring of 196 PTC samples and the analysis of the data of 490 patients from The Cancer Genome Atlas (TCGA) reveled a positive association between the expression of NRG1 and NRF2. Since the presence of NRG1 regulates redox homeostasis through NRF2, protecting PTC cells from the accumulation of ROS and ROS-induced cell death, NRG1 may thus prove to be a potential therapeutic target in the treatment of thyroid cancer.

Original languageEnglish (US)
Pages (from-to)685-693
Number of pages9
JournalInternational journal of oncology
Volume53
Issue number2
DOIs
StatePublished - Aug 2018

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NF-E2-Related Factor 2
Neuregulin-1
Oxidation-Reduction
Homeostasis
Reactive Oxygen Species
Thyroid Neoplasms
Endocrine Gland Neoplasms
Antioxidant Response Elements
MAP Kinase Signaling System
Atlases
Papillary Thyroid cancer
Cell Survival
Glycoproteins
Cell Death
Clone Cells
Western Blotting
Immunohistochemistry
Cell Proliferation
Genome
Therapeutics

Keywords

  • Neuregulin 1
  • Nuclear factor E2-related factor 2
  • Papillary thyroid cancer
  • Redox homeostasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zhang, T. T., Qu, N., Sun, G. H., Zhang, L., Wang, Y., Wang, Y. J., ... Shi, R. L. (2018). NRG1 regulates redox homeostasis via NRF2 in papillary thyroid cancer. International journal of oncology, 53(2), 685-693. https://doi.org/10.3892/ijo.2018.4426

NRG1 regulates redox homeostasis via NRF2 in papillary thyroid cancer. / Zhang, Ting Ting; Qu, Ning; Sun, Guo Hua; Zhang, Long; Wang, Yu; Wang, Yuan Jin; Mu, Xiang Ming; Wei, Wen Jun; Wang, Yu Long; Ji, Qing Hai; Zhu, Yong Xue; Shi, Rong Liang.

In: International journal of oncology, Vol. 53, No. 2, 08.2018, p. 685-693.

Research output: Contribution to journalArticle

Zhang, TT, Qu, N, Sun, GH, Zhang, L, Wang, Y, Wang, YJ, Mu, XM, Wei, WJ, Wang, YL, Ji, QH, Zhu, YX & Shi, RL 2018, 'NRG1 regulates redox homeostasis via NRF2 in papillary thyroid cancer', International journal of oncology, vol. 53, no. 2, pp. 685-693. https://doi.org/10.3892/ijo.2018.4426
Zhang, Ting Ting ; Qu, Ning ; Sun, Guo Hua ; Zhang, Long ; Wang, Yu ; Wang, Yuan Jin ; Mu, Xiang Ming ; Wei, Wen Jun ; Wang, Yu Long ; Ji, Qing Hai ; Zhu, Yong Xue ; Shi, Rong Liang. / NRG1 regulates redox homeostasis via NRF2 in papillary thyroid cancer. In: International journal of oncology. 2018 ; Vol. 53, No. 2. pp. 685-693.
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