ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and c-Myc to reduce breast cancer proliferation

Yuan, Yixuan; Anbalagan, Durkeshwari; Lee, Lay Hoon; Samy, Ramar Perumal; Shanmugam, Muthu K.; Kumar, Alan Prem; Sethi, Gautam; Lobie, Peter E.; Lim, Lina H.K.

doi:10.18632/oncotarget.8875

Cited by 55 publications

(50 citation statements)

References 37 publications

(48 reference statements)

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“…Moreover, miR-196a is highly involved in cancer development, although both positive and negative effects have been shown for cancer progression 26-28. These findings suggest that miR-196a plays an important role during the development and progression of various diseases.…”

Section: Discussionmentioning

confidence: 99%

miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease

Her¹,

Mao²,

Chang³

et al. 2017

Theranostics

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MicroRNAs (miRNAs) play important roles in several neurobiological processes, including the development and progression of diseases. Previously, we identified that one specific miRNA, miR-196a, provides neuroprotective effects on Huntington's disease (HD), although the detailed mechanism is still unclear. Based on our bioinformatic analyses, we hypothesize miR-196a might offer neuroprotective functions through improving cytoskeletons of brain cells. Here, we show that miR-196a could enhance neuronal morphology, further ameliorating intracellular transport, synaptic plasticity, neuronal activity, and learning and memory abilities. Additionally, we found that miR-196a could suppress the expression of RAN binding protein 10 (RANBP10) through binding to its 3' untranslated region, and higher expression of RANBP10 exacerbates neuronal morphology and intracellular transport. Furthermore, miR-196a enhances neuronal morphology through suppressing RANBP10 and increasing the ability of β-tubulin polymerization. Most importantly, we observed higher expression of RANBP10 in the brains of HD transgenic mice, and higher expression of RANBP10 might exacerbate the pathological aggregates in HD. Taken together, we provide evidence that enhancement of neuronal morphology through RANBP10 is one of the neuroprotective mechanisms for miR-196a. Since miR-196a has also been reported in other neuronal diseases, this study might offer insights with regard to the therapeutic use of miR-196a in other neuronal diseases.

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Section: Discussionmentioning

confidence: 99%

miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease

Her¹,

Mao²,

Chang³

et al. 2017

Theranostics

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“…Furthermore, miRs can transcriptionally inhibit the expression of target genes by binding to the 3'-untranslated region (3'-UTR), acting as oncogenes or tumor inhibitors (10). A growing number of studies have indicated that abnormal expression of miRs is associated with human breast cancer (11)(12)(13)(14)(15)(16). Furthermore, mounting evidence indicates that miRs serve key functions in the development of TNBC (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5

Yao

2018

Exp Ther Med

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Abstract. MicroRNA (miR)-146a-5p functions as a tumor suppressor in various types of cancer. However, the role of miR-146a-5p in the development of triple-negative breast cancer (TNBC) is unclear. The present study aimed to investigate the role of miR-146a-5p in TNBC. The expression level of miR-146a-5p in TNBC tissues and cell lines was initially detected using reverse transcription-quantitative polymerase chain reaction. To predict the target gene of miR-146a-5p, TargetScan software was used and a dual luciferase assay was performed to verify the prediction. Furthermore, in order to explore the role of miR-146a-5p in TNBC, miR-146a-5p was overexpressed in TNBC cells using miR-146a-5p mimics. An MTT assay was performed to detect cell proliferation, and a Transwell assay was conducted to determine cell migration and invasion. Furthermore, western blotting was performed to measure associated protein expression. It was revealed that miR-146a-5p was downregulated in TNBC tissues and cell lines. SOX5 was indicated to be a target gene of miR-146a-5p and was upregulated in TNBC cells. Additionally, miR-146a-5p could inhibit TNBC cell proliferation, migration and invasion, repress the expression of mesenchymal markers (N-cadherin, vimentin and fibronectin) and increase epithelial marker (E-cadherin) expression. Furthermore, SOX5 overexpression eliminated the effects of miR-146a-5p mimics on TNBC cells. In conclusion, the data of the present study indicated that miR-146a-5p inhibits the proliferation and metastasis of TNBC cells by regulating SOX5.

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“…ANXA1 has also been shown to inhibit focal adhesions and stress fibre formation which is related to lower adhesion and faster migration [63]. ANXA1 can also regulate the expression of microRNAs such as miR196a, an anti-migratory microRNA, which forms a negative feedback loop to enhance breast cancer migration [65] (Figure 1). In the presence of pro-inflammatory cytokines and other bacterial products, monocytes can differentiate into M1 macrophages phenotype.…”

Section: Resultsmentioning

confidence: 99%

“…Proteomic studies on murine mammary gland cells expressing or lacking ANXA1 revealed that proteins involved in migration and motility were most up-regulated in ANXA1-deficient cells [64] and cells expressing ANXA1 exhibited higher motility and wound healing rates. Further, ANXA1 was shown to increase NF-kB and c-Myc activity leading to the inhibition of microRNA mir196a transcription, inducing a negative feedback loop to promote breast cancer migration and metastasis [53,65], (Figure 1), Similar observations were noted in other tumour cell models, in which ANXA1 was associated with an enhanced migratory profile, as well as elevated mTOR signalling (a central regulator of cell metabolism, proliferation and survival) and matrix metalloproteinase (MMP9) activity, which are important regulators of degradation of the extracellular matrix [63,66].…”

Section: Anxa1 Pro-tumour Evidence In Breast Cancermentioning

confidence: 99%

Annexin A1 in inflammation and breast cancer: a new axis in the tumor microenvironment

Moraes

Ampomah

Lim

2018

Cell Adhesion & Migration

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Targeting inflammation in cancer has shown promise to improve and complement current therapies. The tumor microenvironment plays an important role in cancer growth and metastasis and -tumor associated macrophages possess pro-tumoral and pro-metastatic properties. Annexin A1 (ANXA1) is an immune-modulating protein with diverse functions in the immune system and in cancer. In breast cancer, high ANXA1 expression leads to poor prognosis and increased metastasis. Here, we will review ANXA1 as a modulator of inflammation, and discuss its importance in breast cancer and highlight its new role in alternative macrophage activation in the tumor microenvironment. This review may provide an updated understanding into the various roles of ANXA1 which may enable future therapeutic developments for the treatment of breast cancer.

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ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and c-Myc to reduce breast cancer proliferation

Cited by 55 publications

References 37 publications

miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease

miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease

Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5

Annexin A1 in inflammation and breast cancer: a new axis in the tumor microenvironment

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