miR-21 and let-7 in the Ras and NF-κB Pathways

Choudhury, Saibyasachi N.; Li, Yong

doi:10.2174/2211536611201010065

Cited by 29 publications

(31 citation statements)

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“…MiR-Let-7a may regulate the expression of iNOS and may attenuate the production of nitrite in microglia under inflammatory conditions. Alternatively, studying on translationally suppressed genes targeted by specific miRNA, miRNAs containing let-7 family are generally implicated in regulating TLR/NF-κB signal pathway (Mueller et al, 2014;Choudhury and Li, 2012). SIRT1 known as Sirtuin 1 or NADdependent deacetylase sirtuin-1 has been reported to promote p65 deacetylation and deacetylated p65 to inhibit NF-κB activity and also recently to be identified a target for some kind of miRNAs (Xie et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-Let-7a regulates the function of microglia in inflammation

Cho

Song

et al. 2015

Molecular and Cellular Neuroscience

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Microglia have multiple functions in cerebrovascular and neurodegenerative diseases. Regulation of microglial function during inflammatory stress is important for treatment of central nervous system (CNS) diseases because microglia secrete various substances that affect neurons and glia. MicroRNA-Let-7a (miR-Let-7a) is a tumor suppressor miRNA that has been reported to target transcripts that encode proteins involved in apoptosis. In the present study, we examined the essential role of miR-Let-7a in inflammatory stress by over-expressing miR-Let-7a to investigate its role in determining the BV2 microglial phenotype, a cell line often used as a model of activated microglia. We found that inflammatory factors and Reactive Oxygen Species (ROS) production levels were altered according to miR-Let-7a expression level as measured by Western blot analysis, reverse transcription PCR, quantitative real time PCR, the measurement of nitrite (indicative of the nitric oxide (NO) pathway), and immunocytochemistry (ICC). Our results suggest that miR-Let-7a is involved in the function of microglia in the setting of inflammatory injury. In response to inflammation, miR-Let-7a participates in the reduction of nitrite production and the expression of inducible nitric oxide synthase (iNOS), interleukin (IL)-6 and is involved in increased expression of brain derived neurotrophic factor (BDNF), interleukin (IL)-10, and IL-4 in microglia. Thus, miRNA-Let-7a could act as a regulator of the function of microglia in inflammation.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-Let-7a regulates the function of microglia in inflammation

Cho

Song

et al. 2015

Molecular and Cellular Neuroscience

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“…30,34 KRas was the target gene of let-7 as well as upstream of NF-kB and MAPK/ERK pathway. Based on these observations, we hypothesized that let-7a repressed NF-kB and MAPK/ERK pathway in a KRas-dependent manner.…”

Section: Let-7a Regulates Nf-kb and Mapk/erk Pathway In A Kras-dependmentioning

confidence: 99%

Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells

Xu¹,

Sun²,

Qin

et al. 2015

Cell Cycle

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Keywords: breast cancer stem cells, KRas, let-7a, mammosphere formation capacity, MAPK/ERK, NF-kB Abbreviations: BCSCs, breast cancer stem cells; MFE, mammosphere-forming efficiency Breast cancer stem cells (BCSCs) have the greatest potential to maintain tumorigenesis in all subtypes of tumor cells and were regarded as the key drivers of tumor. Recent evidence has demonstrated that BCSCs contributed to a high degree of resistance to therapy. However, how BCSCs self renewal and tumorigenicity are maintained remains obscure. Herein, our study illustrated that overexpression of let-7a reduced cell proliferation and mammosphere formation ability of breast cancer stem cells(BCSCs) in a KRas-dependent manner through different pathways in vitro and in vivo. To be specific, we provided the evidence that let-7a was decreased, and reversely the expression of KRas was increased with moderate expression in early stages (I/II) and high expression in advanced stages (III/IV) in breast cancer specimens. In addition, the negative correlation between let-7a and KRas was clearly observed. In vitro, we found that let-7a inhibited mammosphere-forming efficiency and the mammosphere-size via NF-kB and MAPK/ERK pathway, respectively. The inhibitory effect of let-7a on mammosphere formation efficiency and the size of mammospheres was abolished after the depletion of KRas. On the contrary, enforced expression of KRas rescued the effect of let-7a. In vivo, let-7a inhibited the growth of tumors, whereas the negative effect of let-7a was rescued after overexpressing KRas. Taken together, our findings suggested that let-7a played a tumor suppressive role in a KRas-dependent manner.

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“…Mechanistic studies suggest that arsenic treatment down-regulates let-7 expression by increasing DNA methylation as treatment with 5-aza-2-deoxycytidine, an inhibitor of DNA methyltransferases, prevents the arsenic-caused decreases of let-7 levels. Consistent with the fact that oncogenic Ras is the target of the let-7 family (Johnson et al, 2005; Choudhury and Li, 2012), Jiang et al (2014) observed that the Ras/NF-κB pathway is activated in arsenic-transformed HaCaT cells, and re-expression of let-7c inhibits the Ras/NF-κB pathway. The findings from this study suggest that down-regulation of let-7 family of miRNAs may play an important role in arsenic-caused transformation of human keratinocytes.…”

Section: The Role Of Mirnas In Metal Carcinogen-induced Cell Maligmentioning

confidence: 65%

The role of microRNAs in metal carcinogen-induced cell malignant transformation and tumorigenesis

Humphries

Wang

Yang

2016

Food and Chemical Toxicology

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MicroRNAs (miRNAs), an important component of epigenetic mechanisms of carcinogenesis, have been shown to play crucial roles in cancer initiation, metastasis, prognosis and responses to drug treatment and may serve as biomarkers for early diagnosis of cancer and tools for cancer therapy. Metal carcinogens, such as arsenic, cadmium, hexavalent chromium and nickel, are well-established human carcinogens causing various cancers upon long term exposure. However, the mechanism of metal carcinogenesis has not been well understood, which limits our capability to effectively diagnose and treat human cancers resulting from chronic metal carcinogen exposure. Over recent years, the role of miRNAs in metal carcinogenesis has been actively explored and a growing body of evidence indicates the critical involvement of miRNAs in metal carcinogenesis. This review aims to discuss recent studies showing that miRNAs play important roles in metal carcinogen-induced cell malignant transformation and tumorigenesis. Some thoughts for future further studies in this field are also presented.

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miR-21 and let-7 in the Ras and NF-κB Pathways

Cited by 29 publications

References 0 publications

MicroRNA-Let-7a regulates the function of microglia in inflammation

MicroRNA-Let-7a regulates the function of microglia in inflammation

Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells

The role of microRNAs in metal carcinogen-induced cell malignant transformation and tumorigenesis

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