Elevated expression of Galectin-3, Thioredoxin and Thioredoxin interacting protein in preeclampsia

AbstractTumour metastasis is a major reason accounting for the poor prognosis of colorectal cancer (CRC), and the discovery of targets in the primary tumours that can predict the risk of CRC metastasis is now urgently needed. In this study, we identified autophagy-related protein 9B (ATG9B) as a key potential target gene for CRC metastasis. High expression of ATG9B in tumour significantly increased the risk of metastasis and poor prognosis of CRC. Mechanistically, we further find that ATG9B promoted CRC invasion mainly through autophagy-independent manner. MYH9 is the pivotal interacting protein for ATG9B functioning, which directly binds to cytoplasmic peptide segments aa368–411 of ATG9B by its head domain. Furthermore, the combination of ATG9B and MYH9 enhance the stability of each other by decreasing their binding to E3 ubiquitin ligase STUB1, therefore preventing them from ubiquitin-mediated degradation, which further amplified the effect of ATG9B and MYH9 in CRC cells. During CRC cell invasion, ATG9B is transported to the cell edge with the assistance of MYH9 and accelerates focal adhesion (FA) assembly through mediating the interaction of endocytosed integrin β1 and Talin-1, which facilitated to integrin β1 activation. Clinically, upregulated expression of ATG9B in human CRC tissue is always accompanied with highly elevated expression of MYH9 and associated with advanced CRC stage and poor prognosis. Taken together, this study highlighted the important role of ATG9B in CRC metastasis by promoting focal adhesion assembly, and ATG9B together with MYH9 can provide a pair of potential therapeutic targets for preventing CRC progression.

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miR-125b enhances metastasis and progression of cancer via the TXNIP and HIF1α pathway in pancreatic cancer

Cancer Biomarkers ◽

10.3233/cbm-203112 ◽

2021 ◽

pp. 1-12

Author(s):

Pengli Wang ◽

Dan Zheng ◽

Hongyang Qi ◽

Qi Gao

Keyword(s):

Pancreatic Cancer ◽

Hypoxia Inducible Factor ◽

Immunofluorescence Assay ◽

Luciferase Assay ◽

Interacting Protein ◽

Over Expression ◽

Thioredoxin Interacting Protein ◽

Cellular Processes ◽

And Migration

BACKGROUND: MicroRNAs (miRNAs) play potential role in the development of various types of cancer conditions including pancreatic cancer (PC) targeting several cellular processes. Present study was aimed to evaluate function of miR-125b and the mechanism involved in PC. METHODS: Cell migration, MTT and BrdU study was done to establish the migration capability, cell viability and cell proliferation respectively. Binding sites for miR-125b were recognized by luciferase assay, expression of protein by western blot and immunofluorescence assay. In vivo study was done by BALB/c nude xenograft mice for evaluating the function of miR-125b. RESULTS: The study showed that expression of miR-125b was elevated in PC cells and tissues, and was correlated to proliferation and migration of cells. Also, over-expression of miR-125b encouraged migration, metastasis and proliferation of BxPC-3 cells, the suppression reversed it. We also noticed that thioredoxin-interacting protein (TXNIP) was the potential target of miR-125b. The outcomes also suggested that miR-125b governed the expression of TXNIP inversely via directly attaching to the 3′-UTR activating hypoxia-inducible factor 1α (HIF1α). Looking into the relation between HIF1α and TXNIP, we discovered that TXNIP caused the degradation and export of HIF1α by making a complex with it. CONCLUSION: The miR-125b-TXNIP-HIF1α pathway may serve useful strategy for diagnosing and treating PC.

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Thioredoxin interacting protein regulates age-associated neuroinflammation

Neurobiology of Disease ◽

10.1016/j.nbd.2021.105399 ◽

2021 ◽

pp. 105399

Author(s):

Saifudeen Ismael ◽

Sanaz Nasoohi ◽

Lexiao Li ◽

Khurram Aslam ◽

Mohammad Moshahid Khan ◽

...

Keyword(s):

Interacting Protein ◽

Thioredoxin Interacting Protein

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Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook

International Journal of Molecular Sciences ◽

10.3390/ijms22052754 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2754

Author(s):

Naila Qayyum ◽

Muhammad Haseeb ◽

Moon Suk Kim ◽

Sangdun Choi

Keyword(s):

Interacting Protein ◽

Thioredoxin Interacting Protein ◽

Signaling Complex ◽

Current Review ◽

Wide Range ◽

Range Of Functions ◽

Species Production ◽

And Oxidative Stress ◽

Significant Attention

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.

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Long Non-coding RNA GAS5 Worsens Coronary Atherosclerosis Through MicroRNA-194-3p/TXNIP Axis

Molecular Neurobiology ◽

10.1007/s12035-021-02332-x ◽

2021 ◽

Author(s):

Yanbing Li ◽

Yu Geng ◽

Boda Zhou ◽

Xuejiao Wu ◽

Ou Zhang ◽

...

Keyword(s):

Endothelial Cells ◽

Coronary Atherosclerosis ◽

Growth Arrest ◽

Interacting Protein ◽

Expression Levels ◽

Thioredoxin Interacting Protein ◽

Non Coding Rna ◽

Proliferation And Apoptosis ◽

Regulatory Effects ◽

Long Non Coding Rna

AbstractIt is formerly conducted that long non-coding RNA growth arrest-specific 5 (GAS5) is involved in the process of coronary atherosclerosis (AS). The regulatory effects of GAS5 on the microRNA (miR)-194-3p/thioredoxin-interacting protein (TXNIP) axis in AS have been insufficiently explored yet. Thereafter, this work is started from GAS5/miR-194-3p/TXNIP axis in AS. AS rats were modeled to obtain their coronary vascular tissues and endothelial cells (ECs), in which GAS5, miR-194-3p, and TXNIP expression were tested. ECs were identified by immunohistochemistry. The mechanism among GAS5, miR-194-3p, and TXNIP was determined. ECs were transfected with inhibited GAS5 or overexpressed miR-194-3p to decipher their functions in proliferation and apoptosis of ECs in AS. Raised GAS5 and TXNIP and degraded miR-194-3p expression levels exhibited in AS. GAS5 bound to miR-194-3p while miR-194-3p targeted TXNIP. Depleting GAS5 or restoring miR-194-3p enhanced proliferation and depressed apoptosis of ECs in AS. This work clearly manifests that inhibited GAS5 facilitates the growth of ECs through miR-194-3p-targeted TXNIP in AS, consolidating the basal reference to the curing for AS.

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