Analysis of Colorectal Carcinogenesis Paradigm between Cold Constitution and Heat Constitution: Earlier ECM Collagen Deposition

Colorectal cancer (CRC) is a common malignant tumor around the world. Studying the unique constitution of CRC patients is conducive to the application of personalized medical treatment for CRC. The most common types of constitution in CRC are cold and heat constitution. A previous study has suggested that the malignant progression in cold and heat constitution CRC are different; however, the mechanism remains unclear. The tumor microenvironment (TME) is likely to vary with each individual constitution, which may affect the tumor growth in different constitutions. The extracellular matrix (ECM), the most important component of TME, plays a critical role in disease progression and outcome in patients with CRC. Moreover, collagen, the major component of the ECM, determines the main functional characteristics of ECM and tissue fibrosis caused by collagen deposition, which is one of the signs of CRC malignant progression. This study aimed to explore the mechanisms leading to different colorectal carcinogenesis paradigms between the cold constitution and heat constitution within the context of ECM collagen deposition. We established the CRC rat models and enrolled 30 CRC patients with cold and heat constitution. The collagen-related parameters were detected by using Sirius red staining combined with polarized light microscope, and expressions of collagen (COL I and COL III) and lysyl oxidase (LOX and LOXL2) were determined using immunohistochemistry, while the mRNA levels of COL1A1, COL3A1, LOX, and LOXL2 were measured by qRT-PCR. We found that a higher degree of collagen deposition in the cold-constitution group. The results suggest cold and heat constitution may affect the colorectal carcinogenesis paradigm by influencing the early collagen deposition in colon tissue. The study may provide an effective idea for clinicians to improve the prognosis of CRC patients with different constitutions.

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The B-Cell Chemoattractant Factor CXCL13 Is Expressed in the Malignant Lymphocyte of the Sezary Syndrome.

Blood ◽

10.1182/blood.v108.11.2292.2292 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2292-2292

Author(s):

Maria Grazia Narducci ◽

Maria Cristina Picchio ◽

Cristina Lazzeri ◽

Irene Angelucci ◽

Enrico Scala ◽

...

Keyword(s):

B Cell ◽

Critical Role ◽

Pcr Analysis ◽

Low Grade ◽

Mrna Levels ◽

Healthy Controls ◽

Qrt Pcr ◽

Cellular Recruitment ◽

Skin Biopsies ◽

Infiltrating Lymphocytes

Abstract Sézary Syndrome (SS) is a rare and aggressive form of Cutaneous T-Cell Lymphoma (CTCL) characterised by a distinct metastatic pattern mainly involving blood and skin. Our expression analyses performed by microarrays demonstrated that many chemokines resulted up-regulated in this type of lymphoma. Since these chemoattractant molecules play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors, we focused our attention on one of them named CXCL13, a lymphoid chemokine involved in B-cell compartmental homing within secondary lymphoid organs. Peripheral Blood Mononuclear cells (PBMCs) were isolated from blood obtained from SS patients and controls by Ficoll-Hypaque density gradient centrifugation (Sigma Aldrich). SS cells and healthy resting CD4+ lymphocytes were purified by positive selection using an anti-human-CD4 conjugated dynabeads (Oxoid). Total RNA was extracted using the Trizol reagent (Life Technologies). Quantitative-Real Time RT-PCR analysis was performed on CD4+ sorted from 14 SS patients and 3 controls. CXCL13 primers were designed by means of the Primer Express software package (Applied Biosystems). The qRT-PCR were performed with a SYBR Green I dye chemistry and AmpliTaq Gold DNA Polymerase on an ABI PRISM 7000 machine (Applied Biosystems). Immunohistochemistry analyses for CXCL13 were performed on formalin-fixed, paraffin-embedded skin biopsies from 15 SS, 15 MF, 6 MF-B cell rich patients using streptoavidin-biotin peroxidase labeling method (DAKO). Sections were counterstained with hematoxylin. Plasma CXCL13 levels were determined using a CXCL13 ELISA kit (BD Pharmingen). Results can be summarized as follow: qRT-PCR analysis revealed that 6 out 13 of SS patients showed an high mRNA levels of CXCL13; Immunohistochemistry analysis showed that CXCL13 is abundantly expressed by neoplastic skin-infiltrating lymphocytes of 9 out 15 SS skin biopsies. Conversely, CXCL13 is weakly expressed on scattered neoplastic skin-infiltrating lymphocytes of 1 out 15 MF and 1 out 6 MF-B cell rich biopsies. Plasma CXCL13 concentrations in SS patients (n = 10) were 1362 ± 134 pg/mL. Conversely, those in MF patients (n = 10) and healthy donors (n = 5) were 70 ± 43 and 13 ± 10 pg/mL, respectively. Compared with healthy controls, plasma CXCL13 levels were significantly higher in patients with SS (p<0.001) and with MF (p=0.04). In this study we report that both circulating and skin-infiltrating neoplastic lymphocytes of SS patients abundantly express CXCL13. Furthermore, this chemokine is also detectable at high level on plasma of SS patients. Conversely, CXCL13 is not observable in healthy controls as well as in Mycosis Fungoides, a variant of low grade of CTCL. These findings indicate that CXCL13 could play a role in pathobiology of Sézary Syndrome and that the expression of this chemokine could be used as diagnostic marker for this kind of tumor

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Abstract 292: Isoform-Specific Expression of Estrogen-Related Receptors Regulates Cardiomyocyte Metabolic Adaptation to Oxidative Stress

Circulation Research ◽

10.1161/res.111.suppl_1.a292 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Kathryn Cribben ◽

Paul McDermott

Keyword(s):

Oxidative Stress ◽

Energy Production ◽

Target Genes ◽

Critical Role ◽

Metabolic Energy ◽

Metabolic Adaptation ◽

Mrna Levels ◽

Fatty Acid Binding ◽

Qrt Pcr ◽

Adult Cardiomyocytes

In the ischemic heart, metabolic adaptation of cardiomyocytes exposed to prolonged hypoxia is critical to sustain myocardial energy production. Metabolic gene expression is regulated by Estrogen-Related Receptor (ERR) transcription factors and Peroxisome Proliferator-Activated Receptor γ Coactivator-1 (PGC-1) co-activators. ERRs do not require ligand to achieve an active conformation and regulate an array of target genes involved in myocardial energy metabolism. These studies aim to determine the regulatory mechanisms governing expression of ERR isoforms (ERRα and ERRβ) in cardiomyocytes undergoing oxidative stress. We hypothesize that metabolic energy production in myocardium initially adapts to hypoxia by inducing transient ERRβ expression, and maintains this compensatory expression through induction of sustained ERRα expression. Adult feline cardiomyocytes in primary culture were electrically stimulated to contract continuously at 1 Hz under normoxia (21% [O2]), hypoxia (0.5% [O2]), or hypoxia followed by reoxygenation. Expression of ERR, PGC-1 and target genes was measured by QRT-PCR (n≥5). QRT-PCR arrays were used to screen for prospective target genes. In response to 24 hours of hypoxia, mRNA levels increased for ERRα (3-fold by 24 hours), ERRβ (11-fold by 12 hours), PGC-1α (16-fold by 24 hours) and PGC-1β (8-fold by 24 hours). Subsequent reoxygenation for 24 hours decreased ERRβ, PGC-1α and PGC-1β mRNA levels to that of normoxia controls. However, reoxygenation did not markedly decrease (∼25%; 0.7 of 3.0-fold) ERRα mRNA levels. Cytochrome C Oxidase Subunit VIc (Cox6c) and Fatty Acid Binding Protein 3 (Fabp3) were identified as potential ERRα target genes in adult cardiomyocytes based on correlation of expression. Moreover, hypoxia-induced increases in Cox6c and Fabp3 mRNA levels were partially blocked by treatment with XCT-790, an inhibitor of ERRα activity. We conclude that hypoxia and subsequent reoxygenation elicit isoform-specific changes in ERR and PGC-1 mRNA expression in adult cardiomyocytes. This observed regulation of expression for ERR isoforms and their target genes may play a critical role in metabolic adaptation to oxidative stress.

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MiR-493 Induces Cytotoxic Autophagy in Prostate Cancer Cells through Regulation on PHLPP2

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200318120733 ◽

2020 ◽

Vol 21 (14) ◽

pp. 1451-1456 ◽

Cited By ~ 2

Author(s):

Jun Deng ◽

Ming Ma ◽

Wei Jiang ◽

Liangliang Zheng ◽

Suping Cui

Keyword(s):

Prostate Cancer ◽

Protein Expression ◽

Cell Function ◽

Mrna Levels ◽

Prostate Cancer Cells ◽

Potent Inducer ◽

Qrt Pcr ◽

Autophagy Gene ◽

The Relationship ◽

Cancer Inhibition

Background: MiR-493 promotes the proliferation of prostate cancer (PC) cells by targeting PHLPP2. We aimed to explore the relationship between miR-493 and autophagy in PC. Methods: qRT-PCR and western blotting were used to determine the mRNA levels and protein expression of miR-493, PHLPP2, autophagy gene BECN1 and ATG7 in PC cells. The autophagy gene expression was determined after PC cells transfected with miR-493 precursor or PHLPP2 precursor. Corresponding changes of autophagy phenotype and PC cell function were also studied. Results: The mRNA levels and protein expression of miR-493, PHLPP2, BECN1 and ATG7 in PC cells were significantly decreased in PC cells. Overexpression of miR-493 or PHLPP2 markedly upregulated the expression levels of BECN1 and ATG7 in PC cells. Overexpression of miR-493 and PHLPP2 markedly promoted autophagy, and inhibited the invasion and cloning formation of PC cells. Conclusion: MiR-493 is a potent inducer of cytotoxic autophagy that leads to prostate cancer inhibition by regulating on PHLPP2.

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Overexpression of Pygo2 Increases Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Cardiomyocyte-like Cells

Current Molecular Medicine ◽

10.2174/1566524019666191017150416 ◽

2020 ◽

Vol 20 (4) ◽

pp. 318-324 ◽

Cited By ~ 3

Author(s):

Lei Yang ◽

Shuoji Zhu ◽

Yongqing Li ◽

Jian Zhuang ◽

Jimei Chen ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Heart Function ◽

Critical Role ◽

Human Umbilical Cord ◽

Stem Cell Markers ◽

Quantitative Real Time Pcr ◽

Qrt Pcr

Background: Our previous studies have shown that Pygo (Pygopus) in Drosophila plays a critical role in adult heart function that is likely conserved in mammals. However, its role in the differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) into cardiomyocytes remains unknown. Objective: To investigate the role of pygo2 in the differentiation of hUC-MSCs into cardiomyocytes. Methods: Third passage hUC-MSCs were divided into two groups: a p+ group infected with the GV492-pygo2 virus and a p− group infected with the GV492 virus. After infection and 3 or 21 days of incubation, Quantitative real-time PCR (qRT-PCR) was performed to detect pluripotency markers, including OCT-4 and SOX2. Nkx2.5, Gata-4 and cTnT were detected by immunofluorescence at 7, 14 and 21 days post-infection, respectively. Expression of cardiac-related genes—including Nkx2.5, Gata-4, TNNT2, MEF2c, ISL-1, FOXH1, KDR, αMHC and α-Actin—were analyzed by qRT-PCR following transfection with the virus at one, two and three weeks. Results : After three days of incubation, there were no significant changes in the expression of the pluripotency stem cell markers OCT-4 and SOX2 in the p+ group hUC-MSCs relative to controls (OCT-4: 1.03 ± 0.096 VS 1, P > 0.05, SOX2: 1.071 ± 0.189 VS 1, P > 0.05); however, after 21 days, significant decreases were observed (OCT-4: 0.164 ± 0.098 VS 1, P < 0.01, SOX2: 0.209 ± 0.109 VS 1, P < 0.001). Seven days following incubation, expression of mesoderm specialisation markers, such as Nkx2.5, Gata-4, MEF2c and KDR, were increased; at 14 days following incubation, expression of cardiac genes, such as Nkx2.5, Gata-4, TNNT2, MEF2c, ISL-1, FOXH1, KDR, αMHC and α-Actin, were significantly upregulated in the p+ group relative to the p− group (P < 0.05). Taken together, these findings suggest that overexpression of pygo2 results in more hUCMSCs gradually differentiating into cardiomyocyte-like cells. Conclusion: We are the first to show that overexpression of pygo2 significantly enhances the expression of cardiac-genic genes, including Nkx2.5 and Gata-4, and promotes the differentiation of hUC-MSCs into cardiomyocyte-like cells.

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Abstract 101: Tissue-specific Deletion of Collectrin in the Proximal Tubular Epithelium Increases Arterial Pressure and Augments Salt-sensitivity

Hypertension ◽

10.1161/hyp.70.suppl_1.101 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Sylvia Cechova ◽

Pei-Lun Chu ◽

Joseph C Gigliotti ◽

Fan Chan ◽

Thu H Le

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Renal Blood Flow ◽

Collecting Duct ◽

Critical Role ◽

Specific Effect ◽

Salt Sensitivity ◽

Kidney Cortex ◽

Mrna Levels ◽

Proximal Tubular

Background: Collectrin ( Tmem27 ) is a key regulator of blood pressure (BP) and modulator of the bioavailability of nitric oxide (NO) and superoxide. It is highly expressed in the kidney in the proximal tubule (PT), collecting duct, and throughout the vascular endothelium. We reported that collectrin plays a critical role as a chaperone for the reabsorption of all amino acids (AAs) in the PT, and for the uptake of the cationic AA L-arginine (L-Arg) in endothelial cells. Global collectrin knockout ( Tmem27 Y/- ) mice display baseline hypertension (HTN), augmented salt-sensitive hypertension (SSH), and decreased renal blood flow. Objective and Methods: To determine the PT-specific effect of collectrin on BP homeostasis and salt sensitivity, we used the Cre -loxP approach and PEPCK-Cre to generate a mouse line lacking collectrin specifically in the PT-- PEPCK-Cre + Tmem27 Y/Flox mice. PEPCK-Cre - Tmem27 Y/Flox mice were used as control. Radiotelemetry was used to measure BP for 2 weeks at baseline and 2 weeks on high salt diet (HSD). Renal blood flow at baseline and on HSD was measured using contrast enhanced ultrasound in the same mice. Results: Successful deletion of collectrin in the PT was confirmed by assessing mRNA levels using real-time RT-PCR, immunohistochemistry staining of renal tissues using anti-collectrin antibody, and quantitation of protein from kidney cortex by Western analysis. Compared to control PEPCK-Cre - Tmem27 Y/Flox mice (n=6), PEPCK-Cre + Tmem27 Y/Flox mice (n=6) displayed significantly higher systolic BP (SBP) at baseline (120.0 ± 2.5 vs 131.6 ± 2.9 mm Hg; p = 0.014) and after HSD (135.3 ± 2.6 vs 151.5 ± 5.2 mm Hg; p = 0.019). Renal blood flow was not different between groups, at baseline nor after HSD. Conclusion: Collectrin in the PT plays an important role in blood pressure homeostasis and response to sodium intake, independent of renal blood flow. Increasing proximal tubular collectrin activity may be a novel therapeutic strategy for the treatment of hypertension and salt-sensitivity.

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miR-26b Regulates Osteoactivin (OA)-Induced Bone Marrow Mesenchymal Cells (BMSCs) Osteogenic Differentiation by Targeting Fms-Like Tyrosine Kinase 3 (FLT3)/AXL

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2742 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1774-1779

Author(s):

Feng Sun ◽

Tianwen Huang ◽

Jianhui Shi ◽

Tianli Wei ◽

Haiwei Zhang

Keyword(s):

Bone Marrow ◽

Bone Formation ◽

Tyrosine Kinase ◽

Osteogenic Differentiation ◽

Signaling Pathway ◽

Formation Process ◽

Mesenchymal Cells ◽

Mrna Levels ◽

Qrt Pcr ◽

Bone Marrow Mesenchymal Cells

Osteoactivin (OA) plays a key role in osteogenic differentiation. miR-26b is elevated in the bone formation process of BMSCs, but whether it is involved in this process is unclear. Bone formation is regulated by FLT3/AXL signaling pathway, which may be a potential target of miR-26b. qRT-PCR detected miR-26b mRNA levels and bone formation-related genes or FLT3/AXL signaling pathway-related genes. Bone formation was analyzed by staining and FLT3/AXL signaling was evaluated along with analysis of miR-26b’s relation with LT3/AXL. miR-26b was significantly elevated in OA-induced bone formation of BMSCs, which can be promoted by miR-26b mimics. When miR-26b was overexpressed, FLT3/AXL signaling pathway was activated. miR-26b can ameliorate Dex-induced osteo-inhibition. miR-26b promotes bone formation of BMSCs by directly targeting FLT3/AXL signaling pathway, suggesting that miR-26b might be a target for inducing osteogenic differentiation.

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Sphingosine kinase 1 regulates lysyl oxidase through STAT3 in hyperoxia-mediated neonatal lung injury

Thorax ◽

10.1136/thoraxjnl-2020-216469 ◽

2021 ◽

pp. thoraxjnl-2020-216469

Author(s):

Alison W Ha ◽

Tao Bai ◽

David L Ebenezer ◽

Tanvi Sethi ◽

Tara Sudhadevi ◽

...

Keyword(s):

Lung Injury ◽

Lysyl Oxidase ◽

Critical Role ◽

Sphingosine Kinase ◽

In Vivo Studies ◽

Sphingosine Kinase 1 ◽

Neonatal Lung ◽

Neonatal Lung Injury

IntroductionNeonatal lung injury as a consequence of hyperoxia (HO) therapy and ventilator care contribute to the development of bronchopulmonary dysplasia (BPD). Increased expression and activity of lysyl oxidase (LOX), a key enzyme that cross-links collagen, was associated with increased sphingosine kinase 1 (SPHK1) in human BPD. We, therefore, examined closely the link between LOX and SPHK1 in BPD.MethodThe enzyme expression of SPHK1 and LOX were assessed in lung tissues of human BPD using immunohistochemistry and quantified (Halo). In vivo studies were based on Sphk1−/− and matched wild type (WT) neonatal mice exposed to HO while treated with PF543, an inhibitor of SPHK1. In vitro mechanistic studies used human lung microvascular endothelial cells (HLMVECs).ResultsBoth SPHK1 and LOX expressions were increased in lungs of patients with BPD. Tracheal aspirates from patients with BPD had increased LOX, correlating with sphingosine-1-phosphate (S1P) levels. HO-induced increase of LOX in lungs were attenuated in both Sphk1−/− and PF543-treated WT mice, accompanied by reduced collagen staining (sirius red). PF543 reduced LOX activity in both bronchoalveolar lavage fluid and supernatant of HLMVECs following HO. In silico analysis revealed STAT3 as a potential transcriptional regulator of LOX. In HLMVECs, following HO, ChIP assay confirmed increased STAT3 binding to LOX promoter. SPHK1 inhibition reduced phosphorylation of STAT3. Antibody to S1P and siRNA against SPNS2, S1P receptor 1 (S1P1) and STAT3 reduced LOX expression.ConclusionHO-induced SPHK1/S1P signalling axis plays a critical role in transcriptional regulation of LOX expression via SPNS2, S1P1 and STAT3 in lung endothelium.

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BMP15 Suppresses Progesterone Production by Down-Regulating StAR via ALK3 in Human Granulosa Cells

Molecular Endocrinology ◽

10.1210/me.2013-1233 ◽

2013 ◽

Vol 27 (12) ◽

pp. 2093-2104 ◽

Cited By ~ 47

Author(s):

Hsun-Ming Chang ◽

Jung-Chien Cheng ◽

Christian Klausen ◽

Peter C. K. Leung

Keyword(s):

Granulosa Cells ◽

Critical Role ◽

Regulatory Protein ◽

Granulosa Cell Tumor ◽

Type I ◽

Mrna Levels ◽

Protein Levels ◽

Human Granulosa Cells ◽

Progesterone Production ◽

Steroidogenic Acute Regulatory

In addition to somatic cell-derived growth factors, oocyte-derived growth differentiation factor (GDF)9 and bone morphogenetic protein (BMP)15 play essential roles in female fertility. However, few studies have investigated their effects on human ovarian steroidogenesis, and fewer still have examined their differential effects or underlying molecular determinants. In the present study, we used immortalized human granulosa cells (SVOG) and human granulosa cell tumor cells (KGN) to compare the effects of GDF9 and BMP15 on steroidogenic enzyme expression and investigate potential mechanisms of action. In SVOG cells, neither GDF9 nor BMP15 affects the mRNA levels of P450 side-chain cleavage enzyme or 3β-hydroxysteroid dehydrogenase. However, treatment with BMP15, but not GDF9, significantly decreases steroidogenic acute regulatory protein (StAR) mRNA and protein levels as well as progesterone production. These suppressive effects, along with the induction of Sma and Mad-related protein (SMAD)1/5/8 phosphorylation, are attenuated by cotreatment with 2 different BMP type I receptor inhibitors (dorsomorphin and DMH-1). Furthermore, depletion of activin receptor-like kinase (ALK)3 using small interfering RNA reverses the effects of BMP15 on SMAD1/5/8 phosphorylation and StAR expression. Similarly, knockdown of ALK3 abolishes BMP15-induced SMAD1/5/8 phosphorylation in KGN cells. These results provide evidence that oocyte-derived BMP15 down-regulates StAR expression and decreases progesterone production in human granulosa cells, likely via ALK3-mediated SMAD1/5/8 signaling. Our findings suggest that oocyte may play a critical role in the regulation of progesterone to prevent premature luteinization during the late stage of follicle development.

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MicroRNA-277 targetsinsulin-like peptides 7and8to control lipid metabolism and reproduction inAedes aegyptimosquitoes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1710970114 ◽

2017 ◽

Vol 114 (38) ◽

pp. E8017-E8024 ◽

Cited By ~ 39

Author(s):

Lin Ling ◽

Vladimir A. Kokoza ◽

Changyu Zhang ◽

Emre Aksoy ◽

Alexander S. Raikhel

Keyword(s):

Lipid Metabolism ◽

Molecular Mechanisms ◽

Fat Body ◽

Critical Role ◽

Target Prediction ◽

Luciferase Reporter ◽

Ovary Development ◽

Mrna Levels ◽

Essential Components ◽

Energy Store

Hematophagous female mosquitoes transmit numerous devastating human diseases, including malaria, dengue fever, Zika virus, and others. Because of their obligatory requirement of a vertebrate blood meal for reproduction, these mosquitoes need a lot of energy; therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. Lipids are the major energy store providing the fuel required for host seeking and reproduction. They are essential components of the fat body, a metabolic tissue that is the insect analog of vertebrate liver and adipose tissue. In this study, we found that microRNA-277 (miR-277) plays an important role in regulating mosquito lipid metabolism. The genetic disruption of miR-277 using the CRISPR-Cas9 system led to failures in both lipid storage and ovary development. miR-277 mimic injection partially rescued these phenotypic manifestations. Examination of subcellular localization of FOXO protein via CRISPR-assisted, single-stranded oligodeoxynucleotide-mediated homology-directed repair revealed that insulin signaling is up-regulated in response to miR-277 depletion. In silico target prediction identified that insulin-like peptides 7 and 8 (ilp7andilp8) are putative targets of miR-277; RNA immunoprecipitation and a luciferase reporter assay confirmed thatilp7andilp8are direct targets of this miRNA. CRISPR-Cas9 depletion ofilp7andilp8led to metabolic and reproductive defects. These depletions identified differential actions of ILP7 and ILP8 in lipid homeostasis and ovarian development. Thus, miR-277 plays a critical role in mosquito lipid metabolism and reproduction by targetingilp7andilp8, and serves as a monitor to control ILP7 and ILP8 mRNA levels.

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Circular RNA Hsa_Circ_0091579 Serves as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000495230 ◽

2018 ◽

Vol 51 (1) ◽

pp. 290-300 ◽

Cited By ~ 18

Author(s):

Chenxing Zhang ◽

Chenyue Zhang ◽

Jiamao Lin ◽

Haiyong Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Tumors ◽

Expression Profiles ◽

Critical Role ◽

Roc Curves ◽

Altered Expression ◽

Qrt Pcr ◽

Specificity And Sensitivity ◽

Tumor Tissues ◽

Potential Biomarker

Background/Aims: An increasing number of studies have suggested that circular RNAs (circRNAs) have vital roles in carcinogenesis and tumor progression. However, the function of circRNAs in hepatocellular carcinoma (HCC) remains poorly characterized. Methods: We investigated the levels of circRNAs in patients with HCC to identify potential diagnostic biomarkers. We examined circRNA expression profiles in liver tumors and paired non-cancerous liver tissues from three HCC patients with cancer thrombus using a circRNA microarray. Bioinformatics analysis was performed to find circRNAs with significantly altered expression levels between tumors and their paired non-tumor tissues. We confirmed our initial findings by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curves were also applied to identify a candidate circRNA with the optimal specificity and sensitivity. Finally, X-tile software was adopted to calculate the most efficient cut-off value for hsa_circ_0091579 expression. Results: Microarray analysis identified 20 unique circRNAs that were differentially expressed between tumor and non-tumor tissues (P < 0.05). The expression of these 20 circRNAs was verified by qRT-PCR. The expression of hsa_circ_16245-1 and hsa_circ_0091579 mRNA was consistent with their levels as tested by the microarray. The ROC curves showed that both hsa_circ_16245-1 and hsa_circ_0091579 had favorable specificity and sensitivity. We further confirmed that hsa_circ_0091579 was significantly upregulated in HCC and its high expression was intimately associated with a worse overall survival in patients with HCC. Conclusion: Hsa_circ_0091579 may play a critical role in HCC progression and serve as a potential biomarker for the prognosis of patients with HCC.

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