Anosmin-1 involved in neuronal cell migration is hypoxia inducible and cancer regulated

Jian, Bixi; Nagineni, Chandrasekharam N.; Meleth, Sreelatha; Grizzle, William E.; Bland, Kirby I.; Chaudry, Irshad H.; Raju, Raghavan

doi:10.4161/cc.8.22.10066

Cited by 25 publications

(32 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with earlier studies in colon, lung and breast cancer (17), our results showed that expression levels of KAL1 were reduced in HCC tissues compared to adjacent noncancerous liver tissues. Furthermore, KAL1 expression was independent of chronic inflammation or fibrosis of the background liver, suggesting that downregulation of KAL1 is a specific event in hepatocarcinogenesis or at later stages.…”

Section: Discussionsupporting

confidence: 82%

“…KAL1, one of the ECM-related proteins, has been reported to have diverse oncological functions (15,17). In the present study, the clinical significance of the expression and methylation status of KAL1 was evaluated in HCC.…”

Section: Discussionmentioning

confidence: 99%

“…However, to date, conflicting results have been reported regarding the onco logical role of KAL1. Decreased KAL1 expression is observed in colon, lung, and ovarian cancers compared with corresponding adjacent normal tissues (17). Conversely, KAL1 over expression promotes brain tumor malignancy through integrin signal pathways and facilitates colon cancer cell migration and antiapoptotic capacity (15).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Translational implication of Kallmann syndrome-1 gene expression in hepatocellular carcinoma

Tanaka

Kanda

Sugimoto

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Accumulation of epigenetic alterations causes inactivation of tumor suppressors and contributes to the initiation and progression of hepatocellular carcinoma (HCC).Identification of methylated genes is necessary to improve our understanding of the pathogenesis of HCC and develop novel biomarkers and therapeutic targets. The Kallmann syndrome-1 (KAL1) gene encodes an extracellular matrixrelated protein with diverse oncological functions. However, the function of KAL1 in HCC has not been examined. We investigated the methylation status of the KAL1 promoter region in HCC cell lines, and evaluated KAL1 mRNA levels and those of genes encoding potential interacting cell adhesion factors. KAL1 mRNA expression level was heterogeneous in nine HCC cell lines, and reactivation of KAL1 mRNA expression was observed in cells with promoter hypermethylation of KAL1 gene after demethylation. In addition, KAL1 mRNA levels inversely correlated with those of ezrin in all nine HCC cell lines. KAL1 expression levels in 144 pairs of surgically-resected tissues were determined and correlated to clinicopathological parameters. KAL1 mRNA level was independent of the background liver status, whereas HCC tissues showed significantly lower KAL1 mRNA levels than corresponding noncancerous liver tissues. Downregulation of KAL1 mRNA in HCC was significantly associated with malignant phenotype characteristics, including elevated tumor markers, larger tumor size, vascular invasion, and hypermethylation of KAL1. Patients with downregulation of KAL1 were more likely to have a shorter overall survival than other patients, and multivariate analysis identified downregulation of KAL1 as an independent prognostic factor (hazard ratio 2.04, 95% confidence interval 1.11-3.90, P=0.022). Our results indicated that KAL1 may act as a putative tumor suppressor in HCC and is inactivated by promoter hypermethylation. KAL1 may serve as a biomarker of malignant phenotype of HCC.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Translational implication of Kallmann syndrome-1 gene expression in hepatocellular carcinoma

Tanaka

Kanda

Sugimoto

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Decreased cellular oxygen results in decreased breakdown and stable cytoplasmic level of Hif-1α. This allows the dimerization of Hif-1α with Hif-1β and binding of the dimer to hypoxia response element (HRE) to recruit transcriptional coactivators (49). The effect of hypoxia in promoting glycolysis while reducing ATP production through decreased mitochondrial oxidation in cardiomyocytes subjected to hypoxia was observed previously in in vitro experiments (11).…”

Section: Discussionmentioning

confidence: 64%

Aging Influences Cardiac Mitochondrial Gene Expression and Cardiovascular Function following Hemorrhage Injury

Jian

Yang

Chen

et al. 2010

Mol Med

Self Cite

View full text Add to dashboard Cite

Cardiac dysfunction and mortality associated with trauma and sepsis increase with age. Mitochondria play a critical role in the energy demand of cardiac muscles, and thereby on the function of the heart. Specific molecular pathways responsible for mitochondrial functional alterations after injury in relation to aging are largely unknown. To further investigate this, 6-and 22-monthold rats were subjected to trauma-hemorrhage (T-H) or sham operation and euthanized following resuscitation. Left ventricular tissue was profiled using our custom rodent mitochondrial gene chip (RoMitochip). Our experiments demonstrated a declined left ventricular performance and decreased alteration in mitochondrial gene expression with age following T-H and we have identified c-Myc, a pleotropic transcription factor, to be the most upregulated gene in 6-and 22-month-old rats after T-H. Following T-H, while 142 probe sets were altered significantly (39 up and 103 down) in 6-month-old rats, only 66 were altered (30 up and 36 down) in 22-month-old rats; 36 probe sets (11 up and 25 down) showed the same trend in both groups. The expression of c-Myc and cardiac death promoting gene Bnip3 were increased, and Pgc1-α and Ppar-α a decreased following T-H. Eleven tRNA transcripts on mtDNA were upregulated following T-H in the aged animals, compared with the sham group. Our observations suggest a cmyc-regulated mitochondrial dysfunction following T-H injury and marked decrease in age-dependent changes in the transcriptional profile of mitochondrial genes following T-H, possibly indicating cellular senescence. To our knowledge, this is the first report on mitochondrial gene expression profile following T-H in relation to aging.

show abstract

“…Our earlier investigations using the RoMitoChip have demonstrated increased expression of the oxygensensing transcription factor, hypoxiainducible factor (Hif)1, alpha subunit (Hif1a), after T-H (19). Elevated c-Myc, together with Hif-1, may also play a role in the suppression of mitochondrial oxidation, in favor of the glycolytic process (19,20,41). However, these pleotropic effectors of energetic balance are likely downstream of SIRT1, since acetylation/ deacetylation of critical proteins including c-Myc may be controlled by SIRT1.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Restores Sirtuin 1 (SIRT1) Activity and Pyruvate Dehydrogenase Kinase 1 (PDK1) Expression after Hemorrhagic Injury in a Rat Model

Jian

Yang

Chaudry

et al. 2013

Mol Med

Self Cite

View full text Add to dashboard Cite

Severe hemorrhage leads to decreased blood flow to tissues resulting in decreased oxygen and nutrient availability affecting mitochondrial function. A mitoscriptome profiling study demonstrated alteration in several genes related to mitochondria, consistent with the mitochondrial functional decline observed after trauma hemorrhage (T-H). Our experiments led to the identification of sirtuin 1 (SIRT1) as a potential target in T-H. Administration of resveratrol (a naturally occurring polyphenol and activator of SIRT1) after T-H improved left ventricular function and tissue ATP levels. Our hypothesis was that mitochondrial function after T-H depends on SIRT1 activity. In this study, we evaluated the activity of SIRT1, a mitochondrial functional modulator, and the mitochondrialglycolytic balance after T-H. We determined the changes in protein levels of pyruvate dehydrogenase kinase (PDK)-1 and nuclear c-Myc, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and NF-E2-related factor (NRF)2 after T-H and after treatment with resveratrol or a combination of sirtinol (a SIRT1 inhibitor) and resveratrol. We have also tested the activity of mitochondrial complex 1. SIRT1 enzyme activity was significantly decreased after T-H, whereas resveratrol treatment restored the activity. We found elevated PDK1 and c-Myc levels and decreased PGC-1α, NRF2 and mitochondrial complex I activity after T-H. The reduced SIRT1 activity after T-H may be related to declining mitochondrial function, since resveratrol was able to reinstate SIRT1 activity and mitochondrial function. The elevated level of PDK1 (an inhibitor of pyruvate dehydrogenase complex) after T-H indicates a possible shift in cellular energetics from mitochondria to glycolysis. In conclusion, SIRT1 modulation alters left ventricular function after T-H through regulation of cellular energetics.

show abstract

Anosmin-1 involved in neuronal cell migration is hypoxia inducible and cancer regulated

Cited by 25 publications

References 23 publications

Translational implication of Kallmann syndrome-1 gene expression in hepatocellular carcinoma

Translational implication of Kallmann syndrome-1 gene expression in hepatocellular carcinoma

Aging Influences Cardiac Mitochondrial Gene Expression and Cardiovascular Function following Hemorrhage Injury

Resveratrol Restores Sirtuin 1 (SIRT1) Activity and Pyruvate Dehydrogenase Kinase 1 (PDK1) Expression after Hemorrhagic Injury in a Rat Model

Contact Info

Product

Resources

About