MiR-200, a new star miRNA in human cancer

Feng, Xiangling; Wang, Zhengming; Fillmore, Rebecca A.; Xi, Yaguang

doi:10.1016/j.canlet.2013.11.004

Cited by 311 publications

(279 citation statements)

References 107 publications

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“…Bioinformatics search 12,13 for miRNA-responsive elements in the FUS 3 0 -UTR indicated that among the identified 3 0 -UTR mutations 7 , two patients carried the G48A substitution (in one case of inherited type), which localizes to a predicted binding site for miR-141 and miR-200a. These two miRNAs share the same seed sequence and belong to the same miRNA family 14 The members of this family are of particular interest for human health and disease, because they have been shown to be downregulated during tumour progression and to act as key regulators of epithelial-to-mesenchymal transition 15 .…”

Section: Resultsmentioning

confidence: 99%

An ALS-associated mutation in the FUS 3′-UTR disrupts a microRNA–FUS regulatory circuitry

et al. 2014

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While the physiologic functions of the RNA-binding protein FUS still await thorough characterization, the pathonegetic role of FUS mutations in amyotrophic lateral sclerosis (ALS) is clearly established. Here we find that a human FUS mutation that leads to increased protein expression, and was identified in two ALS patients with severe outcome, maps to the seed sequence recognized by miR-141 and miR-200a in the 3 0 -UTR of FUS. We demonstrate that FUS and these microRNAs are linked by a feed-forward regulatory loop where FUS upregulates miR-141/200a, which in turn impact FUS protein synthesis. We also show that Zeb1, a target of miR-141/200a and transcriptional repressor of these two microRNAs, is part of the circuitry and reinforces it. Our results reveal a possible correlation between deregulation of this regulatory circuit and ALS pathogenesis, and open interesting perspectives in the treatment of these mutations through ad hoc-modified microRNAs.

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Section: Resultsmentioning

confidence: 99%

An ALS-associated mutation in the FUS 3′-UTR disrupts a microRNA–FUS regulatory circuitry

et al. 2014

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“…However, it is not clear how TSHR suppresses EMT. Previous studies have demonstrated that microRNA (miRNA/miR) serves an important role in EMT; for example, miR-146b-5p induces EMT through the regulation of Wnt/β-catenin signaling (19,20) and the miR-200 family inhibits polycomb complex protein BMI1, and zinc finger E-box-binding homeobox 1 and 2, to suppress EMT (21)(22)(23). Further studies are required to demonstrate whether TSHR regulates EMT through miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Downregulated expression of TSHR is associated with distant metastasis in thyroid cancer

Liu

Men

et al. 2017

Oncol Lett

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Abstract. In differentiated thyroid cancer (DTC), the association between thyroid-stimulating hormone receptor (TSHR) and metastasis, and the underlying molecular mechanisms remain unclear. The role of TSHR in the epithelial-mesenchymal transition (EMT) has not yet been reported, to the best of our knowledge. In the present study, the role of TSHR in the distant metastasis of DTC was investigated. TSHR was significantly downregulated in well-differentiated thyroid cancer cells and tissues, and a lack of TSHR promoted thyroid cancer cell invasion and metastasis by inhibiting the EMT of thyroid cancer cells. In addition, the prognostic value of TSHR in thyroid cancer was analyzed. Immunohistochemical analysis of 172 DTC tissues revealed that a lack of expression of TSHR was associated with distant metastasis and a poor survival rate. Multivariate analyses demonstrated that TSHR expression was a significant prognostic factor for distant metastasis and survival time. The results from the present study demonstrated that TSHR inhibits metastasis through regulating EMT in vitro, and that a lack of expression of TSHR is a significant independent factor affecting distant metastasis and poor prognosis in DTC.

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“…At the same time, activation of protein kinase C and ERK by sublytic MAC doses (48) also sets into motion mortalin-dependent release of MAC from cells attacked by complement (16). miR-200 family members are major regulators of epithelialmesenchymal transition (49) and are believed to be generally involved in cancer progression, metastasis, and chemoresistance (50). Downregulation of miR-200 family members was proposed to be essential for progression and invasiveness of breast (51,52) and ovarian cancer, and its high expression is associated with improved survival of ovarian (53) and pancreatic cancer patients (54).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Complement-Dependent Cytotoxicity by MicroRNAs miR-200b, miR-200c, and miR-217

Hillman

Mazkereth

Farberov

et al. 2016

The Journal of Immunology

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The impact of microRNAs (miRNAs) known to regulate numerous biologic processes on complement-dependent cytotoxicity (CDC) was investigated in K562 cells. The C5b-9 complex is the executioner of CDC. Cells protect themselves from CDC by C5b-9 elimination, a process involving the mitochondrial chaperone mortalin/GRP75. Potential miR-200 (b and c) and miR-217 regulatory sites were identified in mortalin mRNA. Overexpression of miR-200b/c or miR-217 lowered the expression of mortalin mRNA. miRNA inhibitors for miR-200b, miR-200c, or miR-217 enhanced mortalin mRNA level. Unexpectedly, these miRNA modulators had no significant effect on mortalin protein level. Metabolic labeling analysis demonstrated that, to compensate for reduction in mortalin mRNA level, the cells increased the rate of synthesis of mortalin protein. Cells overexpressing miR-200b/c or miR-217 showed reduced sensitivity to CDC, whereas inhibition of miR-200c and miR-217 enhanced cell death. miR-200b/c overexpression reduced C5b-9 binding and enhanced its release from the cells and promoted mortalin relocation to the plasma membrane. Inhibition of miR-200 (b and c) and miR-217 had no effect on the expression level of the membrane complement-regulatory proteins CD46, CD55, and CD59. However, overexpression of miR-200b/c or miR-217 enhanced expression of CD46 and CD55 (not of CD59). Overall, the data demonstrate miRNA regulation of cell sensitivity to CDC. We identified miR-200b, miR-200c, and miR-217 as regulators of mortalin and, perhaps indirectly, of CD46 and CD55. Cell exposure to a sublytic dose of complement was shown to increase expression of miR-200 (b and c), suggesting that complement C5b-9 exerts a feedback-regulatory effect on these miRNAs.

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MiR-200, a new star miRNA in human cancer

Cited by 311 publications

References 107 publications

An ALS-associated mutation in the FUS 3′-UTR disrupts a microRNA–FUS regulatory circuitry

An ALS-associated mutation in the FUS 3′-UTR disrupts a microRNA–FUS regulatory circuitry

Downregulated expression of TSHR is associated with distant metastasis in thyroid cancer

Regulation of Complement-Dependent Cytotoxicity by MicroRNAs miR-200b, miR-200c, and miR-217

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