miR-320 targets transferrin receptor 1 (CD71) and inhibits cell proliferation

Schaar, Dale; Medina, Daniel; Moore, Dirk F.; Strair, Roger; Yi, Tao

doi:10.1016/j.exphem.2008.10.002

Cited by 115 publications

(70 citation statements)

References 47 publications

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“…With the help of bioinformatics-based databases (25-28) and published reports (12,13), the search was narrowed down to miR320a as a possible modulator of AQP1 and AQP4. Recent studies have established miR-320a as an inhibitor of the cell cycle gene (POLR3D) and the transferrin receptor gene (TFRC) (4,29). Our AQP1 and AQP4 gene expression profiles were similar FIGURE 2.…”

Section: Discussionsupporting

confidence: 50%

MicroRNA 320a Functions as a Novel Endogenous Modulator of Aquaporins 1 and 4 as Well as a Potential Therapeutic Target in Cerebral Ischemia*

Sepramaniam

Armugam

Lim

et al. 2010

Journal of Biological Chemistry

142

112

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Aquaporins facilitate efficient diffusion of water across cellular membranes, and water homeostasis is critically important in conditions such as cerebral edema. Changes in aquaporin 1 and 4 expression in the brain are associated with cerebral edema, and the lack of water channel modulators is often highlighted. Here we present evidence of an endogenous modulator of aquaporin 1 and 4. We identify miR-320a as a potential modulator of aquaporin 1 and 4 and explore the possibility of using miR-320a to alter the expression of aquaporin 1 and 4 in normal and ischemic conditions. We show that precursor miR-320a can function as an inhibitor, whereas anti-miR-320a can act as an activator of aquaporin 1 and 4 expressions. We have also shown that antimiR-320a could bring about a reduction of infarct volume in cerebral ischemia with a concomitant increase in aquaporins 1 and 4 mRNA and protein expression. MicroRNAs (miRNAs)2 regulate mRNA expression by binding to the 3Ј-UTR (1). As simple as it sounds, identifying targets for miRNAs remains a challenging task mainly because each miRNA has hundreds of mRNA targets (2). Increasing this complexity are emerging reports on miRNAs binding at 5Ј-UTR as well as promoter regions (3-5). Recent studies also reveal the possibility of miRNAs functioning as transcriptional or splicing regulators within the nucleus (6) and being involved in genetic exchange via exosomes with adjacent cells (7). Because of this complexity in regulation, of the hundreds of miRNAs identified in the human species, only a handful have been assigned their specific targets.Comparison of miRNA profiles between normal and diseased samples allows the identification of crucial miRNAs that are altered during disease conditions and enables one to search for possibilities of altering these expression profiles in an attempt to normalize or reduce the patho-physiological conditions of the disease. Changes in the expression of miRNAs have been reported in several diseases (8 -10) including cerebral ischemia (11-13). Cerebral ischemia is a highly debilitating condition, and ischemia-induced edema further increases complications and morbidity (14). The movement of water into and out of an ischemic brain is thought to be mainly modulated by aquaporins (AQPs), especially aquaporin 1 (AQP1) and aquaporin 4 (AQP4). AQPs are a family of transmembrane proteins involved in transport of water, glycerol, ions, and even CO 2 (15, 16). The 13-member family is ubiquitously expressed in almost all parts of the human body. Often more than one homolog is found to be present in any tissue or organ. In the brain AQP1, 3, 4, 5, 8, and 9 have been reported, with AQP1, 4, and 9 being expressed abundantly (17). The importance of AQP1 and AQP4 regulation in edema has been highlighted in several studies (18,19). AQP4 knockouts in mice showed increased protection against cytotoxic edema caused by water intoxication and permanent focal cerebral ischemia, whereas in conditions leading to vasogenic brain edema, it had a deleterious effect (18,19). s...

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Section: Discussionsupporting

confidence: 50%

MicroRNA 320a Functions as a Novel Endogenous Modulator of Aquaporins 1 and 4 as Well as a Potential Therapeutic Target in Cerebral Ischemia*

Sepramaniam

Armugam

Lim

et al. 2010

Journal of Biological Chemistry

142

112

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“…miR-320 expression levels were found to be downregulated in primary breast cancer (BC) (20) and intrahepatic cholangiocarcinoma (21). miR-320 expression also inhibited HL-60 cell proliferation by targeting transferrin receptor 1 (CD71) (22).…”

Section: Introductionmentioning

confidence: 99%

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

Zhang

Liu

et al. 2011

Oncol Rep

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Abstract. MicroRNAs (miRNAs) have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that various miRNAs function as oncogenes or tumor suppressors in colorectal cancer (CRC), the role of miRNAs in mediating liver metastasis remains unexplored. The expression profile of miRNAs in liver metastasis and primary CRC tissues was analyzed by miRNA microarrays and verified by real-time polymerase chain reaction (PCR). In 62 CRC patients, the expression levels of miR-320a were determined by real-time PCR, and the effects on migration and invasion of miR-320a were determined using a transwell assay. miR-320a target genes were confirmed by luciferase assay, real-time PCR and Western blot analysis. A set of miRNAs was found to be dysregulated in the liver metastasis tissues compared to matched primary CRC tissues, and the expression levels of miR-320a were significantly decreased in the liver metastasis tissues examined. miR-320a was correlated with tumor progression in CRC. miR-320a was downregulated in liver metastatic colon cancer cells and inhibited liver metastatic colon cancer cell migration and invasion. miR-320a directly binds to the 3'UTR of neuropilin 1 (NRP-1), a protein that functions as a co-receptor of vascular epithelial growth factor. miR-320a downregulated the expression of NRP-1 at both the mRNA and protein levels. These data demonstrated that miR-320a may be useful for identifying CRC patients that are at an elevated risk for developing liver metastasis. Our findings suggest that miR-320a may be a novel therapeutic candidate for the treatment of colorectal cancer.

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“…As no increase in cell death was observed with miR-320 overexpression, the lower cell number was likely due to decreased cell division, an effect of PP2A activity. Thus far 3 targets have been verified for miR-320: the PTEN component ETS2 [17], histone deacetylase 4 [18], and the transferrin receptor CD71 [19]. None of these targets have been implicated in neurite outgrowth, but ETS2 is required for breast cell proliferation [20] and CD71 enhances proliferation in B-cell lymphoma cells [21].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-320 induces neurite outgrowth by targeting ARPP-1

White¹,

Giffard²

2012

NeuroReport

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MicroRNAs are important in central nervous system development, functioning, and pathophysiology. Here we demonstrate that increasing levels of microRNA 320 (miR-320) for 3 days markedly increases neurite length and at 4 days reduces total cell number in N2A cells. In silico analysis of possible miR-320 targets identified cAMP-regulated phosphoprotein-19 kDa (ARPP-19) and semaphorin 3a (Sema3a) as potential targets that could be involved. ARPP-19 was validated by demonstrating reduced mRNA and protein levels when miR-320 was overexpressed, while miR-320 had no effect on Sema3a expression. ARPP-19 is known to inhibit protein phosphatase-2A (PP2A) activity, which inhibits mitosis and induces neurite outgrowth, making this the likely mechanism. Thus increased levels of miR-320 leads to decreased levels of ARPP-19, increased neurite length, and fewer total cells. These data suggest that miR-320 could play a role in neuronal development and might be a target to enhance neuronal regeneration following injury.

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miR-320 targets transferrin receptor 1 (CD71) and inhibits cell proliferation

Cited by 115 publications

References 47 publications

MicroRNA 320a Functions as a Novel Endogenous Modulator of Aquaporins 1 and 4 as Well as a Potential Therapeutic Target in Cerebral Ischemia*

MicroRNA 320a Functions as a Novel Endogenous Modulator of Aquaporins 1 and 4 as Well as a Potential Therapeutic Target in Cerebral Ischemia*

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

MicroRNA-320 induces neurite outgrowth by targeting ARPP-1

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