MDA-7/IL-24 regulates the miRNA processing enzyme DICER through downregulation of MITF

Pradhan, Anjan K.; Bhoopathi, Praveen; Talukdar, Sarmistha; Scheunemann, Danielle; Sarkar, Devanand; Cavenee, Webster K.; Das, Swadesh K.; Emdad, Luni; Fisher, Paul B.

doi:10.1073/pnas.1819869116

Cited by 27 publications

(20 citation statements)

References 52 publications

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“…Accumulating evidence has demonstrated that miRNAs are involved in cell proliferation, migration, and invasion in malignancy, such as lung cancer bone metastasis 11,13,14,17,19 . For instance, HE et al 29 revealed that downregulation of miR-20b may dramatically suppress H22 cell proliferation by directly targeting PTEN.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNAs/miRs) are endogenous, small, noncoding and highly conserved RNAs 11,12 . Recent studies have revealed that miRNAs are implicated in various cellular processes [13][14][15] . In addition, many studies have already demonstrated that miRNA dysfunction is involved in the occurrence and progression of malignancies, such as breast cancer, gastric carcinoma, prostate cancer, and lung cancer [16][17][18][19] .…”

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confidence: 99%

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miR-192-5p suppresses the progression of lung cancer bone metastasis by targeting TRIM44

Zou

Zhu

Lian

et al. 2019

Sci Rep

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Lung cancer is the leading cause of cancer-related deaths worldwide, with 50-70% of patients suffering from bone metastasis. Accumulating evidence has demonstrated that miRNAs are involved in cell proliferation, migration, and invasion in malignancy, such as lung cancer bone metastasis. In the present study, we demonstrated that reduced miR-192-5p and increased TRIM44 levels were associated with the proliferation, migration and invasion of lung cancer. Furthermore, the potential functions of miR-192-5p were explored in A549 and NCI-H1299 cells. We found that miR-192-5p upregulation suppressed tumour behaviours in lung cancer cells. To further investigate whether miR-192-5p is associated with TRIM44, we used TargetScan software to predict the binding site between miR-192-5p and TRIM44. Luciferase activity assays were performed to verify this prediction. In addition, the significant role of miR-192-5p in negatively regulating TRIM44 expression was manifested by our research group. our results suggest that miR-192-5p inhibited the proliferation, migration and invasion of lung cancer through TRIM44.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

miR-192-5p suppresses the progression of lung cancer bone metastasis by targeting TRIM44

Zou

Zhu

Lian

et al. 2019

Sci Rep

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“…In 2019, one novel study showed that melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), a multifunctional cytokine, displayed broad-spectrum anticancer activity by regulating the function of DICER. This study provides a new anticancer method in which key miRNA enzymes, such as DICER, are targeted to disrupt miRNA synthesis in cancer cells (28).…”

Section: Biogenesis Of Mir-27a In Solid Tumorsmentioning

confidence: 99%

MicroRNA-27a (miR-27a) in Solid Tumors: A Review Based on Mechanisms and Clinical Observations

Zhang

Cao

et al. 2019

Front. Oncol.

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MicroRNAs (miRNAs) are a family of highly conserved, non-coding single-stranded RNAs transcribed as ~70 nucleotide precursors to an 18–22 nucleotide product (1). miRNAs can silence their homologous target genes at the post-transcriptional level, and these genes have been revealed to play an important role in tumorigenesis, invasion and metastasis (2). MicroRNA-27a (miR-27a), transcripted by miR-27a gene, has proved to implicate with many kinds of solid tumors, showing potential as a useful biomarker or drug target for clinical application. However, even though miR-27a has been reported in many cancers, the mechanism and signal pathways of miR-27 in oncogenesis, invasion, and metastasis are still obscure. Moreover, recent studies show that miR-27a pays an important role in epithelial-mesenchymal-transition, regulating tumor immune response, and chemoresistance. In this review, we summarize the current literature, demonstrate the established link between miR-27a and tumorigenesis, and focus on recently identified mechanisms. The review also aims to demonstrate the potential of miR-27a as a diagnostic and/or prognostic biomarker in solid tumors and to discuss the possibilities of targeted therapy and drug design.

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“…MDA-7/IL-24 induces the expression of the chaperone protein BiP/GRP78, which in turn results in endoplasmic reticulum (ER) stress and cell death [16]. Additionally, this cytokine regulates toxic autophagy through a miR-221-Beclin-1 axis [17, 18]. MDA-7/IL-24 also has anti-angiogenic activity and it inhibits invasion and metastasis of cancer cells (1).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking

et al. 2019

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Melanoma differentiation associated gene-7 ( mda-7/IL-24 ) is a member of the IL-10 family of cytokines, with ubiquitous direct and “bystander” tumor-selective killing properties. MDA-7/IL-24 protein binds distinct type II cytokine heterodimeric receptor complexes, IL-20R1/IL-20R2, IL-22R1/IL-20R1 and IL-22R1/IL-20R2. Recombinant MDA-7/IL-24 protein induces endogenous mda-7/IL-24 expression in a receptor-dependent manner; since A549 cells that lack a complete set of cognate receptors are not responsive to exogenous protein. The mechanism of MDA-7/IL-24 ligand-receptor biology is not well understood. We explored the interaction of MDA-7/IL-24 with its’ receptors and the consequences of ligand-receptor docking. Using both pharmacological and genetic approaches we demonstrate that MDA-7/IL-24 internalization employs the clathrin-mediated endocytic pathway leading to degradation of receptors via the lysosomal/ubiquitin proteosomal pathway. This clathrin-mediated endocytosis is dynamin-dependent. This study resolves a novel mechanism of MDA-7/IL-24 protein “bystander” function, which involves receptor/protein-mediated internalization and receptor degradation.

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MDA-7/IL-24 regulates the miRNA processing enzyme DICER through downregulation of MITF

Cited by 27 publications

References 52 publications

miR-192-5p suppresses the progression of lung cancer bone metastasis by targeting TRIM44

miR-192-5p suppresses the progression of lung cancer bone metastasis by targeting TRIM44

MicroRNA-27a (miR-27a) in Solid Tumors: A Review Based on Mechanisms and Clinical Observations

Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking

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