Intermediaries of branched chain amino acid metabolism induce fetal hemoglobin, and repress SOX6 and BCL11A, in definitive erythroid cells

Karkashon, Shay; Raghupathy, Radha; Bhatia, Himanshu; Dutta, Abhishek; Hess, Sonja; Higgs, Jaimie; Tifft, Cynthia J.; Little, Jane A.

doi:10.1016/j.bcmd.2015.05.006

Cited by 5 publications

(2 citation statements)

References 60 publications

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“…Second, SOX6 could be targeted by some microRNAs, such as miR‐1269, miR‐208, miR‐155, and miR‐212‐3p, 42‐45 which could regulate SOX6 expression through translation repression. Ubiquitylation or histone modification might also be involved in the inactivation of SOX6 46,47 . Further studies are required to shed light on the detailed regulation mechanisms of SOX6 expression in ccRCC.…”

Section: Discussionmentioning

confidence: 99%

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

Chen

Xie

et al. 2020

Molecular Carcinogenesis

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Sex‐determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor‐related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss‐of‐function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β‐catenin signaling as well as its target genes, c‐Myc and cyclin D1. Interesting, the tumor‐suppressive function of SOX6 was proved to be dependent on its specific high‐mobility‐group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β‐catenin signaling pathway in an HMG domain‐dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.

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Section: Discussionmentioning

confidence: 99%

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

Chen

Xie

et al. 2020

Molecular Carcinogenesis

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“…A previous report demonstrated an increasement of Hb, ferritin, red blood cell count and hematocrit in training athletes after daily consumption of an amino acid mixture, which encompassed all three BCAAs (33). Intermediaries of BCAA metabolism are also known to induce fetal Hb during definitive erythropoiesis (34).…”

Section: Discussionmentioning

confidence: 99%

Branched-chain amino acids are linked with iron metabolism

Enko¹,

Moro²,

Holasek³

et al. 2020

Ann Transl Med

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Background: The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are reported to influence erythropoiesis and the human iron status. Large study cohorts encompassing biomarkers of iron metabolism and BCAAs are still lacking. Methods:We investigated potential interactions between blood concentrations of all three BCAAs valine, leucine and isoleucine and biomarkers of iron metabolism [i.e., hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), iron, transferrin, ferritin, transferrin saturation, soluble transferrin receptor (sTfR)] in 430 outpatients referred for a medical health check-up. Linear regression models were performed to assess possible associations between variables.Results: All three BCAAs were positively correlated with Hb, ferritin and the sTfR (r-values: 0.145-0.382; P values: <0.001-0.003). The strongest correlation was observed between valine and Hb (r=0.382; P value <0.001). Linear regression models showed a statistically significant influence of all three BCAAs on Hb and ferritin (β-coefficients: 0.173-0.351; all P values: <0.001). Seventeen patients with anemia (4%) were found with significantly lower serum BCAA concentrations compared to 413 non-anemic individuals (P<0.05).Conclusions: These data indicate a pathophysiological link between the three BCAAs valine, leucine and isoleucine and the human iron indicators Hb and ferritin. Further studies are needed to clarify the exact causal mechanisms of these findings.

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Chiral resolution of plasma amino acids reveals enantiomer-selective associations with organ functions

et al. 2022

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Intermediaries of branched chain amino acid metabolism induce fetal hemoglobin, and repress SOX6 and BCL11A, in definitive erythroid cells

Cited by 5 publications

References 60 publications

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

Branched-chain amino acids are linked with iron metabolism

Chiral resolution of plasma amino acids reveals enantiomer-selective associations with organ functions

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