scholarly journals MicroRNAs as Diagnostic Tools in Hepatocellular Carcinoma

2021 ◽  
Vol 3 (4) ◽  
pp. 237-246
Author(s):  
Jessica Evangelista ◽  
Elisa Zaninotto ◽  
Annalisa Gaglio ◽  
Michele Ghidini ◽  
Lucrezia Raimondi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Small Sample Size ◽  
Expression Patterns ◽  
Critical Role ◽  
Measurement Techniques ◽  
Small Sample ◽  
Diagnostic Tools ◽  
Migration And Invasion ◽  
Altered Expression ◽  
Liver Cancers

Liver cancer is the fourth leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 80% of all liver cancers. The serum concentration of alpha-fetoprotein (AFP) is the only validated biomarker for HCC diagnosis. MicroRNAs (miRNAs) are small non-coding RNAs of 21–30 nucleotides playing a critical role in human carcinogenesis, with types of miRNAs with oncogenic (oncomiRs) or tumor suppressor features. The altered expression of miRNAs in HCC is associated with many pathological processes, such as cancer initiation, tumor growth, apoptosis escape, promotion of migration and invasion. Moreover, circulating miRNAs have been increasingly investigated as non-invasive biomarkers for HCC diagnosis. MiRNAs’ expression patterns are altered in HCC and several single miRNAs or miRNAs panels have been found significantly up or downregulated in HCC with respect to healthy controls or non-oncological patients (cirrhotic or with viral hepatitis). However, any of the investigated miRNAs or miRNAs panels has entered clinical practice so far. This has mostly to do with lack of protocols standardization, small sample size and discrepancies in the measurement techniques. This review summarizes the major findings regarding the diagnostic role of miRNAs in HCC and their possible use together with standard biomarkers in order to obtain an early diagnosis and easier differential diagnosis from non-cancerous liver disease.

scholarly journals A meta-analysis on environmental drivers of marine phytoplankton C : N : P

2019 ◽  
Author(s):  
Tatsuro Tanioka ◽  
Katsumi Matsumoto
Keyword(s):  
Small Sample Size ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Critical Role ◽  
Small Sample ◽  
Marine Phytoplankton ◽  
Environmental Drivers ◽  
Carbon Export ◽  
Elemental Stoichiometry ◽  
C And N

Abstract. The elemental stoichiometry of marine phytoplankton plays a critical role in the global carbon cycle through carbon export. Although extensive laboratory experiments have been carried out over the years to assess the influence of different environmental drivers on the elemental composition of phytoplankton, a comprehensive quantitative assessment of the processes is still lacking. Here, we synthesized the responses of P : C and N : C ratios of marine phytoplankton to five major drivers (phosphate and nitrate, irradiance, temperature, and iron) by meta-analysis of laboratory experimental data available in the literature. Our results show that the response of the ratios to changes in macronutrients is consistent across all the studies, where the nutrient availability is positively related to changes in P : C and N : C ratios. We found that diatoms are more sensitive to the changes in macronutrients compared to other eukaryotes and cyanobacteria, possibly due to their larger cell size and their abilities to quickly regulate their gene expression patterns required for nutrient uptake. The effect of irradiance on P : C was mixed and not significant, but the same effect on N : C was significant and constant across all studies where an increase in irradiance decreased N : C. The response to temperature changes was mixed by species, except warming consistently decreased P : C ratio in cyanobacteria. This may explain why P : C is consistently low in the cyanobacteria-dominated subtropical oceans. The effect of iron on P : C and N : C for cyanobacteria were statistically significant but the small sample size precludes drawing firm conclusions. Overall, our findings highlight the high stoichiometric plasticity of diatoms and the importance of macronutrients in determining P : C and N : C ratios, which both provide us insights on how to understand and model plankton diversity and productivity.

Abstract W P73: Feasibility and Preliminary Results of Whole Blood RNA-Sequencing Analysis in Patients With Intracranial Aneurysms

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Blake Haas ◽  
Nestor R Gonzalez ◽  
Elina Nikkola ◽  
Mark Connolly ◽  
William Hsu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Rna Sequencing ◽  
Whole Blood ◽  
Intracranial Aneurysms ◽  
Small Sample Size ◽  
Expression Patterns ◽  
Small Sample ◽  
Cellular Respiration ◽  
Sequencing Analysis

Introduction: Intracranial aneurysms (IA) growth and rupture have been associated with chronic remodeling of the arterial wall. However, the pathobiology of this process remains poorly understood. The objective of the present study was to evaluate the feasibility of analyzing gene expression patterns in peripheral blood of patients with ruptured and unruptured saccular IAs. Materials and Methods: We analyzed human whole blood transcriptomes by performing paired-end, 100 bp RNA-sequencing (RNAseq) using the Illumina platform. We used STAR to align reads to the genome, HTSeq to count reads, and DESeq to normalize counts across samples. Self-reported patient information was used to correct expression values for ancestry, age, and sex. We utilized weighted gene co-expression network analysis (WGCNA) to identify gene expression network modules associated with IA size and rupture. The DAVID tool was employed to search for Gene Ontology enrichment in relevant modules. Results: Samples from 12 patients (9 females, age 57.6 +/-12) with IAs were analyzed. Four had ruptured aneurysms. RNA isolation and application of the methodology described above was successful in all samples. Although the small sample size prevents us from drawing definite conclusions, we observed promising novel co-expression networks for IAs: WCGNA analysis showed down-regulation of two transcript modules associated with ruptured IA status (r=-0.78, p=0.008 and r=-0.77, p=0.009), and up-regulation of two modules associated with aneurysm size (r=0.86, p=0.002 and r=0.9, p=4e-04), respectively. DAVID analyses showed that genes upregulated in an IA size-associated module were enriched with genes involved in cellular respiration and translation, while genes involved in transcription were down-regulated in a module associated with ruptured IAs. Conclusions: Whole blood RNAseq analysis is a feasible tool to capture transcriptome dynamics and achieve a better understanding of the pathophysiology of IAs. Further longitudinal studies of patients with IAs using network analysis are justified.

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

2018 ◽  
Vol 51 (1) ◽  
pp. 290-300 ◽  
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.

scholarly journals Efficient prediction of a spatial transcriptomics profile better characterizes breast cancer tissue sections without costly experimentation

2021 ◽  
Author(s):  
Taku Monjo ◽  
Masaru Koido ◽  
Satoi Nagasawa ◽  
Yutaka Suzuki ◽  
Yoichiro Kamatani
Keyword(s):  
Breast Cancer ◽  
Small Sample Size ◽  
Expression Patterns ◽  
Imputation Accuracy ◽  
Gene Clusters ◽  
Small Sample ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Gene Expressions ◽  
Tissue Sections

Spatial transcriptomics is an emerging technology requiring costly reagents and considerable skills, limiting the identification of transcriptional markers related to histology. Here, we show that predicted spatial gene-expressions in unmeasured regions and tissues can enhance biologists' histological interpretations. We developed the Deep learning model for Spatial gene Clusters and Expression, DeepSpaCE and confirmed its performance using the spatial-transcriptome profiles and immunohistochemistry images of consecutive human breast cancer tissue sections. For example, the predicted expression patterns of SPARC, an invasion marker, highlighted a small tumor-invasion region that is difficult to identify using raw data of spatial transcriptome alone because of a lack of measurements. We further developed semi-supervised DeepSpaCE using unlabeled histology images and increased the imputation accuracy of consecutive sections, enhancing applicability for a small sample size. Our method enables users to derive hidden histological characters via spatial transcriptome and gene annotations, leading to accelerated biological discoveries without additional experiments.

scholarly journals Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qun Dai ◽  
Jingyi Deng ◽  
Jinrong Zhou ◽  
Zhuhong Wang ◽  
Xiao-feng Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Marked Rise ◽  
Hcc Cells

Abstract Background Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. Methods The expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo. Results We found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2. Conclusion TUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.

scholarly journals A Critical Role for ZDHHC2 in Metastasis and Recurrence in Human Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Chuanhui Peng ◽  
Zhijun Zhang ◽  
Jian Wu ◽  
Zhen Lv ◽  
Jie Tang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Portal Vein ◽  
Tumor Size ◽  
Chromosomal Region ◽  
Critical Role ◽  
Migration And Invasion ◽  
Metastatic Recurrence ◽  
Tumor Thrombi

It has been demonstrated that loss of heterozygosity (LOH) was frequently observed on chromosomes 8p22-p23 in hepatocellular carcinoma (HCC) and was associated with metastasis and prognosis of HCC. However, putative genes functioning on this chromosomal region remain unknown. In this study, we evaluated LOH status of four genes on 8p22-p23 (MCPH1, TUSC3, KIAA1456, and ZDHHC2). LOH on ZDHHC2 was associated with early metastatic recurrence of HCC following liver transplantation and was correlated with tumor size and portal vein tumor thrombi. Furthermore, our results indicate that ZDHHC2 expression was frequently decreased in HCC. Overexpression of ZDHHC2 could inhibit proliferation, migration, and invasion of HCC cell line Bel-7402in vitro. These results suggest an important role for ZDHHC2 as a tumor suppressor in metastasis and recurrence of HCC.

scholarly journals Autophagic Inhibition of Caveolin-1 by Compound Phyllanthus urinaria L. Activates Ubiquitination and Proteasome Degradation of β-catenin to Suppress Metastasis of Hepatitis B-Associated Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Danping Huang ◽  
Bowen Yang ◽  
Yaoyao Yao ◽  
Mianmian Liao ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Late Phase ◽  
Critical Role ◽  
Migration And Invasion ◽  
Caveolin 1 ◽  
Proteasome Degradation ◽  
Phyllanthus Urinaria

Compound Phyllanthus urinaria L. (CP) is a traditional Chinese medicine (TCM) formula for cancer treatment in the clinic, particularly during progression of hepatitis B-associated hepatocellular carcinoma (HBV-associated HCC). Nevertheless, its anti-metastatic action and mechanisms are not well elucidated. In this study, CP was found to exert remarkable inhibitory effects on the proliferation, migration and invasion of HBV-associated HCC cells. The following network and biological analyses predicted that CP mainly targeted Caveolin-1 (Cav-1) to induce anti-metastatic effects, and Wnt/β-catenin pathway was one of the core mechanisms of CP action against HBV-associated HCC. Further experimental validation implied that Cav-1 overexpression promoted metastasis of HBV-associated HCC by stabilizing β-catenin, while CP administration induced autophagic degradation of Cav-1, activated the Akt/GSK3β-mediated proteasome degradation of β-catenin via ubiquitination activation, and subsequently attenuated the metastasis-promoting effect of Cav-1. In addition, the anti-cancer and anti-metastatic action of CP was further confirmed by in vivo and ex vivo experiments. It was found that CP inhibited the tumor growth and metastasis of HBV-associated HCC in both mice liver cancer xenograft and zebrafish xenotransplantation models. Taken together, our study not only highlights the novel function of CP formula in suppressing metastasis of HBV-associated HCC, but it also addresses the critical role of Cav-1 in mediating Akt/GSK3β/β-catenin axis to control the late-phase of cancer progression.

scholarly journals Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells

2017 ◽  
Vol 41 (4) ◽  
pp. 1584-1595 ◽  
Author(s):  
Tao Ye ◽  
Jing Xu ◽  
Ling Du ◽  
Wenhui Mo ◽  
Yiming Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Migration And Invasion ◽  
Biological Traits ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
E Cadherin

Background/Aims: Dysregulation of ubiquitin-associated protein 2-like (UBAP2L) has been reported in tumors, but its role in hepatocellular carcinoma (HCC) progression is unclear. Methods: The expression levels of UBAP2L in HCC tissues and HCC cell lines were detected by western blot and quantitative real-time (qRT) PCR. The effects of UBAP2L expression on HCC cell biological traits, including migration and invasion, were investigated by wound healing assay and matrigel transwell assay. Simultaneously, the expression of epithelial-mesenchymal transition (EMT) markers including E-cadherin, CK-18, N-cadherin, Vimentin, Claudin7 and the promoter activity of E-cadherin were detected by western blot and qRT-PCR. Subsequently, role of SNAIL1 in UBAP2L-mediated EMT and the mechanism underlying UBAP2L-mediated SNAIL1 expression were further investigated. Results: UBAP2L was overexpressed in human HCC tissues compared with peri-tumoral tissues. Downregulation of UBAP2L inhibited migration, invasion and the EMT in highly metastatic HCC cell lines. Furthermore, UBAP2L knockdown inhibited expression of the transcriptional repressor SNAIL1 and its ability to bind to the E-cadherin promoter via SMAD2 signaling pathway, which in turn resulted in increased E-cadherin expression. Additionally, bioinformatics analysis showed that expression of UBAP2L is correlated with poor prognosis in patients with HCC. Conclusions: UBAP2L plays a critical role in maintenance of the metastatic ability of HCC cells via SNAIL1 Regulation and is predictive of a poor clinical outcome.

scholarly journals ZC3H13 Inhibits the Progression of Hepatocellular Carcinoma through m6A-PKM2-Mediated Glycolysis and Enhances Chemosensitivity

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Qibo Wang ◽  
Haichuan Xie ◽  
Hao Peng ◽  
Jianjian Yan ◽  
Limin Han ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Stability ◽  
Critical Role ◽  
Prognostic Significance ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Epigenetic Modulation ◽  
Gain Loss ◽  
Hcc Cells

Objective. N6-Methyladenosine (m6A) is the most prevalent RNA epigenetic modulation in eukaryotic cells, which serves a critical role in diverse physiological processes. Emerging evidences indicate the prognostic significance of m6A regulator ZC3H13 in hepatocellular carcinoma (HCC). Herein, this study was conducted for revealing biological functions and mechanisms of ZC3H13 in HCC. Methods. Expression of ZC3H13 was examined in collected HCC and normal tissues, and its prognostic significance was investigated in a public database. Gain/loss of functional assays were presented for defining the roles of ZC3H13 in HCC progression. The specific interactions of ZC3H13 with PKM2 were validated in HCC cells via mRNA stability, RNA immunoprecipitation, and luciferase reporter and MeRIP‐qPCR assays. Moreover, rescue experiments were carried out for uncovering the mechanisms. Results. ZC3H13 expression was downregulated in HCC, and its loss was in relation to dismal survival outcomes. Functionally, overexpressed ZC3H13 suppressed proliferation, migration, and invasion and elevated apoptotic levels of HCC cells. Moreover, ZC3H13 overexpression sensitized to cisplatin and weakened metabolism reprogramming of HCC cells. Mechanically, ZC3H13-induced m6A modified patterns substantially abolished PKM2 mRNA stability. ZC3H13 facilitated malignant behaviors of HCC cells through PKM2-dependent glycolytic signaling. Conclusion. Collectively, ZC3H13 suppressed the progression of HCC through m6A-PKM2-mediated glycolysis and sensitized HCC cells to cisplatin, which offered a fresh insight into HCC therapy.

Sign in / Sign up

Export Citation Format

Share Document