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Loss of macrophage migration inhibitory factor impairs the growth properties of human HeLa cervical cancer cells.

ABSTRACT: OBJECTIVES:? This study aims to determine the role of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine associated with cell proliferation and tumour growth in vivo. MATERIALS AND METHODS:? Our team used RNA interference technology to knock down MIF expression in human HeLa cervical cancer cells and to establish a stable cell line lacking MIF function. RESULTS:? Our results showed that long-term loss of MIF had little effect on cell morphology, but significantly inhibited their population growth and proliferation. The HeLa MIF-knockdown cells retained normal apoptotic signalling pathways in response to TNF-alpha treatment; however, they exhibited unique DNA profiles following doxorubicin treatment, suggesting that MIF may regulate a cell cycle checkpoint upon DNA damage. Our data also showed that knockdown of MIF expression in HeLa cells led to increased cell adhesion and therefore impaired their migratory capacity. More importantly, cells lacking MIF failed to either proliferate in soft agar or form tumours in vivo, when administered to nude mice. CONCLUSION:? MIF plays a pivotal role in proliferation and tumourigenesis of human HeLa cervical carcinoma cells, and may represent a promising therapeutic target for cancer intervention.

SUBMITTER: Xiao DZ

PROVIDER: S-EPMC6495722 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Loss of macrophage migration inhibitory factor impairs the growth properties of human HeLa cervical cancer cells.

Xiao D Z DZ Dai B B Chen J J Luo Q Q Liu X Y XY Lin Q X QX Li X H XH Huang W W Yu X Y XY

Cell proliferation 20111013 6

<h4>Objectives</h4> This study aims to determine the role of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine associated with cell proliferation and tumour growth in vivo.<h4>Materials and methods</h4> Our team used RNA interference technology to knock down MIF expression in human HeLa cervical cancer cells and to establish a stable cell line lacking MIF function.<h4>Results</h4> Our results showed that long-term loss of MIF had little effect on cell morphology, but si ...[more]

PMID: 21991924

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Project description:Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes monocyte/macrophage-activation responses by increasing the expression of Toll-like receptors and inhibiting activation-induced apoptosis. On the basis of results of previous genetic linkage studies and reported altered innate immune response in autism spectrum disorder, we hypothesized that MIF could represent a candidate gene for autism spectrum disorder or its diagnostic components.Genetic association between autism spectrum disorder and MIF was investigated in 2 independent sets of families of probands with autism spectrum disorder, from the United States (527 participants from 152 families) and Holland (532 participants from 183 families). Probands and their siblings, when available, were evaluated with clinical instruments used for autism spectrum disorder diagnoses. Genotyping was performed for 2 polymorphisms in the promoter region of the MIF gene in both samples sequentially. In addition, MIF plasma analyses were conducted in a subset of Dutch patients from whom plasma was available.There were genetic associations between known functional polymorphisms in the promoter for MIF and autism spectrum disorder-related behaviors. Also, probands with autism spectrum disorder exhibited higher circulating MIF levels than did their unaffected siblings, and plasma MIF concentrations correlated with the severity of multiple autism spectrum disorder symptoms.These results identify MIF as a possible susceptibility gene for autism spectrum disorder. Additional research is warranted on the precise relationship between MIF and the behavioral components of autism spectrum disorder, the mechanism by which MIF contributes to autism spectrum disorder pathogenesis, and the clinical use of MIF genotyping.

Dataset Information

Loss of macrophage migration inhibitory factor impairs the growth properties of human HeLa cervical cancer cells.

Publications

Loss of macrophage migration inhibitory factor impairs the growth properties of human HeLa cervical cancer cells.

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