MIF is a 3’ flap nuclease that facilitates DNA replication and promotes tumor growth

Wang, Yijie; Chen, Yan; Wang, Chenliang; Yang, Mingming; Bao, Lei; Wang, Jennifer E.; Kim, Bong Woo; Chan, Kara Y.; Xu, Weizhi; Capota, Emanuela; Ortega, Janice; Nijhawan, Deepak; Li, Guo Min; Luo, Weibo

doi:10.1038/s41467-021-23264-z

Cited by 27 publications

(15 citation statements)

References 59 publications

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“…MCM2-7 proteins are present in proliferating cells (43) and overexpression of MCM2, MCM4 and MCM6 is associated with tumorigenesis (44)(45)(46). DNA POL α, δ, and ε are key mediators of DNA replication in eukaryotes (41); their mutation or abnormal expression affects the occurrence, development and invasion of human colorectal cancer, stomach adenocarcinoma and pancreatic adenocarcinoma (47)(48)(49). POLD1 encodes DNA POL δ (50); an increase in its protein expression or activity has been demonstrated to be associated with tumorigenesis in colorectal carcinoma and endometrial carcinoma (51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

Cadherin‑16 inhibits thyroid carcinoma cell proliferation and invasion

Yang

Liu

et al. 2022

Oncol Lett

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, a member of the cadherin family of adhesion molecules, serves an important role in the formation and maintenance of the thyroid follicular lumen. Decreased expression of CDH16 has been reported to be associated with tumor stage in papillary thyroid cancer (PTC); however, previous analyses have been limited and the biological role of CDH16 in different subtypes of TC is unknown. To investigate the role of CDH16 in the occurrence and development of TC, bioinformatic analysis of three TC subtypes (PTC, follicular cell-derived TC and anaplastic TC) was performed using an extended data set from the Gene Expression Omnibus database, with additional confirmation using data from The Cancer Genome Atlas, as well as biopsies from 35 patients with PTC and TC or follicular cell lines. According to the dataset analysis, CDH16 was downregulated in PTC and follicular cell-derived and anaplastic TC; the downregulation in PTC was independent of DNA copy number variation. Furthermore, low expression levels of CDH16 were significantly correlated with tumor size, lymph node metastasis status and disease stage in 35 patients with PTC. Gene Set Enrichment Analysis suggested that CDH16 participated in DNA replication and cell adhesion pathways. To evaluate CDH16 activity, CDH16 was overexpressed in TC-derived BCPAP cells. CDH16 overexpression inhibited cell proliferation, migration and invasion and induced apoptosis by downregulating proteins associated with DNA replication and cell adhesion. These results support the identification of CDH16 as a valuable target for TC prognosis and therapy and, to the best of our knowledge, represent the first direct demonstration of its mechanistic role in TC.

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Section: Discussionmentioning

confidence: 99%

Cadherin‑16 inhibits thyroid carcinoma cell proliferation and invasion

Yang

Liu

et al. 2022

Oncol Lett

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“…However, MIF was recently reported to function intracellularly and independently of any of these receptors as a nuclease regulating DNA replication (Wang et al, 2021), thus potentially promoting tumor growth in another cell-intrinsic manner. Accordingly, we compared proliferation rates of MIF-KO/KD and MIF-WT sarcoma cells in vitro.…”

Section: Myeloid Cells Promote Tumor Growth In a Soft-tissue Sarcoma ...mentioning

confidence: 99%

Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity

Tessaro¹,

Ko²,

Simone³

et al. 2022

Cell Reports

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“…MIF shares a redox-active Cys-Xaa-Xaa-Cys (CXXC) motif with thiol-protein oxidoreductases (TPORs) such as thioredoxin and glutaredoxin and has been implicated in cellular redox regulation and antioxidative mechanisms in ischemic cardiomyocytes [70][71][72][73]. Moreover, recent evidence suggests that nuclear translocation of MIF following ischemic cell stress is linked to MIF-nuclease activity that contributes to cell death programs such as parthanatos [74,75]. The nuclease activity appears to be independent of the CXXC motif and tautomerase pocket, but rather dependent on a conserved PD-(D/E)XK motif known for metal-dependent nucleases [74].…”

Section: Macrophage Migration-inhibitory Factor (Mif)-a Key Modulator...mentioning

confidence: 99%

A cross‐kingdom view on the immunomodulatory role of MIF/D‐DT proteins in mammalian and plant Pseudomonas infections

Panstruga

Donnelly

2022

Immunology

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Gram-negative Pseudomonas bacteria are largely harmless saprotrophs, but some species can be potent pathogens of both plants and mammals. Macrophage migration-inhibitory factor (MIF) and its homologue D-dopachrome tautomerase (D-DT, also referred to as MIF-2) are multifunctional proteins that in addition to their intracellular functions also serve as extracellular signalling molecules (cytokines) in orchestrating mammalian immune responses. It recently emerged that plants also possess MIF-like proteins, termed MIF/D-DT-like (MDL) proteins. We here provide a comparative cross-kingdom view on the immunomodulatory role of MIF and MDL proteins during Pseudomon as infections in mammals and plants. Although in both kingdoms the lack of MIF/MDL proteins is associated with a reduction in bacterial load and disease symptoms, the underlying molecular principles seem to be different. We provide a perspective for future research activities to unravel additional commonalities and differences in the MIF/MDLmediated adjustment of antibacterial immune activities. K E Y W O R D S cross-kingdom, D-dopachrome tautomerase, macrophage migration-inhibitory factor, plant, Pseudomonas bacteria PSEUDOMONADS -COSMOPOLITAN GRAM-NEGATIVE BACTERIAPseudomonas is a genus of metabolically versatile, Gramnegative, aerobic bacilli that have one or several polar flagellae. The taxon, which belongs to the phylum proteobacteria, class gammaproteobacteria and family Pseudomonaceae, comprises more than 140 species, rendering it the genus with the highest number of species within the group of Gram-negative bacteria [1].

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MIF is a 3’ flap nuclease that facilitates DNA replication and promotes tumor growth

Cited by 27 publications

References 59 publications

Cadherin‑16 inhibits thyroid carcinoma cell proliferation and invasion

Cadherin‑16 inhibits thyroid carcinoma cell proliferation and invasion

Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity

A cross‐kingdom view on the immunomodulatory role of MIF/D‐DT proteins in mammalian and plant Pseudomonas infections

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