Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers - PubMed (original) (raw)

Review

Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers

Yiting Chen et al. Front Oncol. 2020.

Abstract

Thioredoxin-interacting protein (TXNIP) is a thioredoxin-binding protein that can mediate oxidative stress, inhibit cell proliferation, and induce apoptosis by inhibiting the function of the thioredoxin system. TXNIP is important because of its wide range of functions in cardiovascular diseases, neurodegenerative diseases, cancer, diabetes, and other diseases. Increasing evidence has shown that TXNIP expression is low in tumors and that it may act as a tumor suppressor in various cancer types such as hepatocarcinoma, breast cancer, and lung cancer. TXNIP is known to inhibit the proliferation of breast cancer cells by affecting metabolic reprogramming and can affect the invasion and migration of breast cancer cells through the TXNIP-HIF1α-TWIST signaling axis. TXNIP can also prevent the occurrence of bladder cancer by inhibiting the activation of ERK, which inhibits apoptosis in bladder cancer cells. In this review, we find that TXNIP can be regulated by binding to transcription factors or other binding proteins and can also be downregulated by epigenetic changes or miRNA. In addition, we also summarize emerging insights on TXNIP expression and its functional role in different kinds of cancers, as well as clarify its participation in metabolic reprogramming and oxidative stress in cancer cells, wherein it acts as a putative tumor suppressor gene to inhibit the proliferation, invasion, and migration of different tumor cells as well as promote apoptosis in these cells. TXNIP may therefore be of basic and clinical significance for finding novel molecular targets that can facilitate the diagnosis and treatment of malignant tumors.

Keywords: TXNIP (thioredoxin interacting protein); cancer; clinical significance; oxidative stress; research progress.

Copyright © 2020 Chen, Ning, Cao, Wang, Du, Jiang, Feng and Zhang.

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Figures

Figure 1

Figure 1

Mechanisms of TXNIP regulation. TXNIP expression can be negatively affected by (b) transcription factors (c-myc,et), (c) epigenetic changes [histone deacetylase 1 (HDAC1), et], (a) miRNAs (miR-373, et) and can be positively affected by (d) binding proteins, such as ChREBP.

Figure 2

Figure 2

Functions of TXNIP involved in several typical cancers. (A) TXNIP participates in different signaling pathways to inhibit the proliferation and migration of PDAC, RC, and other cancer cells; (B) miR-373 drives the transformation and metastasis of breast cancer by the TXNIP/HIF1α/TWIST signaling axis; (C) Knocking down NRF2 can promote the cycle arrest of PCA cells by increasing the expression level of TXNIP; (D) TXNIP participates in different signaling pathways to promote the apoptosis of cancer cells such as AML and lung cancer.

Figure 3

Figure 3

TXNIP acts as a tumor suppressor gene: TXNIP inhibits tumor cell proliferation and promotes tumor cell apoptosis by participating in metabolic reprogramming and oxidative stress; ⊝ signs indicate TXNIP-negative interaction.

References

    1. Ludwig DL, Kotanides H, Le T, Chavkin D, Bohlen P, Witte L. Cloning, genetic characterization, and chromosomal mapping of the mouse VDUP1 gene. Gene. (2001) 269:103–12. 10.1016/S0378-1119(01)00455-3 - DOI - PubMed
    1. Nishiyama A, Matsui M, Iwata S, Hirota K, Masutani H, Nakamura H, et al. Identification of thioredoxin-binding protein-2/vitamin D(3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression. J Biol Chem. (1999) 274:21645–50. 10.1074/jbc.274.31.21645 - DOI - PubMed
    1. Chung J-W, Jeon J-H, Yoon S-R, Choi I. Vitamin D3 upregulated protein 1 (VDUP1) is a regulator for redox signaling and stress-mediated diseases. Dermatol. (2006) 33:662–9. 10.1111/j.1346-8138.2006.00156.x - DOI - PubMed
    1. Filhoulaud G, Guilmeau S, Dentin R, Girard J, Postic C. Novel insights into ChREBP regulation and function. Trends Endocrinol Metab. (2013) 24:257–68. 10.1016/j.tem.2013.01.003 - DOI - PubMed
    1. Lu J, Holmgren A. Thioredoxin system in cell death progression. Antioxid Redox Signal. (2012) 17:1738–47. 10.1089/ars.2012.4650 - DOI - PubMed

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