Functional significance of erythropoietin in renal cell carcinoma

Morais, Christudas; Johnson, David W.; Vesey, David A.; Gobé, Glenda C.

doi:10.1186/1471-2407-13-14

Cited by 36 publications

(32 citation statements)

References 87 publications

(73 reference statements)

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“…Although the upregulation of Ki‐67 expression is associated with neck metastasis, recurrence, and poor survival, some studies report a lack of association between Ki‐67 expression and survival . The hypoxia‐responsive hematopoietic factor, erythropoietin, is one of the molecules regulated by HIF . Erythropoietin and EPOR expression are associated with poor prognosis in patients with cancer .…”

Section: Discussionmentioning

confidence: 99%

HIF‐1α and CA‐IX as predictors of locoregional control for determining the optimal treatment modality for early‐stage laryngeal carcinoma

Kwon

Park

et al. 2014

Head & Neck

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Section: Discussionmentioning

confidence: 99%

HIF‐1α and CA‐IX as predictors of locoregional control for determining the optimal treatment modality for early‐stage laryngeal carcinoma

Kwon

Park

et al. 2014

Head & Neck

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“…EPO is widely used to treat tumor-related anemia, however, the effect of EPO on RCC has not been well delineated (19). Several studies observed that exogenous recombinant human EPO inhibits cancer progression, however, other studies indicated that it promotes cancer progression (20)(21)(22).…”

Section: Fbp1 Expression --------------------------------------------mentioning

confidence: 99%

Association between FBP1 and hypoxia-related gene expression in clear cell renal cell carcinoma

Ning¹,

Teng²,

Gong³

et al. 2016

Oncology Letters

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Abstract. Fructose-1,6-bisphosphatase 1 (FBP1) is a rate-limiting enzyme in gluconeogenesis. Recently, the catalytic activity-independent function of FBP1, hypoxia-induced factor (HIF) repression in the nucleus, was identified. The aim of the present study was to investigate the association between FBP1 and hypoxia-related gene expression in clear cell renal cell carcinoma (ccRCC). The protein expression levels of FBP1, HIF-1α, HIF-2α, erythropoietin (EPO) and carbonic anhydrase IX (CA9) were assessed by immunohistochemical staining of ccRCC paraffin blocks from 123 patients using the tissue microarray technique. The expression level of FBP1 was then correlated with various clinicopathological factors, and the protein expression levels of HIF-1α, HIF-2α, EPO and CA9. Clinicopathological factors, including age, gender, T stage and Fuhrman grade, were not significantly different between patients with low and high FBP1 expression in ccRCC (P>0.05). FBP1 protein expression level was significantly correlated with the expression levels of HIF-1α (P=0.005) and EPO (P= 0.010), but not significantly correlated with the expression levels of HIF-2α (P=0.123) and CA9 (P=0.513) in ccRCC tissues. The current findings confirm the association between FBP1 and hypoxia-related gene expression, and may facilitate understanding of the mechanisms of ccRCC tumorigenesis.

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“…cancers including hepatocellular carcinoma 42,43 . EPO may also stimulate epithelialmesenchymal transition (EMT) associated with cancer progression 44 .…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Inflammation-Induced Expression and Secretion of MicroRNA 122 Leads to Reduced Blood Levels of Kidney-Derived Erythropoietin and Anemia

et al. 2016

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BACKGROUND AIM Anemia is commonly associated with acute and chronic inflammation, but the mechanisms of their interaction are not clear. We investigated whether microRNA 122 (MIR122), which is generated in the liver and is secreted into the blood, is involved in the development of anemia associated with inflammation. METHODS We characterized the primary transcript of the human liverspecific MIR122 using northern blot, quantitative real-time PCR, and 3' and 5' RACE analyses. We studied regulation of MIR122 in human hepatocellular carcinoma (HCC) cell lines (Huh7 and HepG2) as well as in C57BL/6 and mice with disruption of the tumor necrosis factor gene (Tnf). Liver tissues were collected and analyzed by bioluminescence imaging or immunofluorescence. Inflammation in mice was induced by lipopolysaccharide (LPS) or by cerulein injections. Mice were given 4 successive injections of LPS, leading to inflammation-induced anemia. Steatohepatitis was induced with a choline-deficient high-fat diet. Hemolytic anemia was stimulated by phenylhydrazine injection. MIR122 was inhibited in mice by tail-vein injection of antogomiR-122 (an oligonucleotide antagonist of MIR122). MicroRNA and mRNA levels were determined by quantitative real time PCR. RESULTS The primary transcript of MIR122 spanned 5 kb, comprising 3 exons; the third encodes MIR122. Within the MIR122 promoter region we identified a nuclear factor-B (NF-B) binding site and demonstrated that RELA, as well as activators of NF-B (TNF and LPS), increased promoter activity of MIR122. Administration of LPS to mice induced secretion of MIR122 into blood, which required TNF. Secreted MIR122 reached the kidney and reduced expression of erythropoietin (Epo), which we identified as a MIR122 target gene. Injection of mice with antagomiR-122 increased blood levels of EPO, reticulocytes, and hemoglobin. We found an inverse relationship between blood levels of MIR122 and EPO in mice with acute pancreatitis or steatohepatitis, and also in patients with acute inflammation. CONCLUSION In mice, we found that LPS-induced inflammation increases blood levels of MIR122, which reduces expression of Epo in the kidney; this is a mechanism of inflammation-induced anemia. Strategies to block MIR122 in patients with inflammation could reduce the development or progression of anemia. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT AbstractBackground & Aim: Anemia is commonly associated with acute and chronic inflammation, but the mechanisms of their interaction are not clear. We investigated whether microRNA 122 (MIR122),...

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Functional significance of erythropoietin in renal cell carcinoma

Cited by 36 publications

References 87 publications

HIF‐1α and CA‐IX as predictors of locoregional control for determining the optimal treatment modality for early‐stage laryngeal carcinoma

HIF‐1α and CA‐IX as predictors of locoregional control for determining the optimal treatment modality for early‐stage laryngeal carcinoma

Association between FBP1 and hypoxia-related gene expression in clear cell renal cell carcinoma

Inflammation-Induced Expression and Secretion of MicroRNA 122 Leads to Reduced Blood Levels of Kidney-Derived Erythropoietin and Anemia

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