scholarly journals Transcriptomic Analysis of mRNA-lncRNA-miRNA Interactions in Hepatocellular Carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xia Tang ◽  
Delong Feng ◽  
Min Li ◽  
Jinxue Zhou ◽  
Xiaoyuan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Rna Seq ◽  
Pairwise Interactions ◽  
Micro Rnas ◽  
Non Coding Rnas ◽  
First Time

Abstract Fully elucidating the molecular mechanisms of non-coding RNAs (ncRNAs), including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), underlying hepatocarcinogenesis is challenging. We characterized the expression profiles of ncRNAs and constructed a regulatory mRNA-lncRNA-miRNA (MLMI) network based on transcriptome sequencing (RNA-seq) of hepatocellular carcinoma (HCC, n = 9) patients. Of the identified miRNAs (n = 203) and lncRNAs (n = 1,090), we found 16 significantly differentially expressed (DE) miRNAs and three DE lncRNAs. The DE RNAs were highly enriched in 21 functional pathways implicated in HCC (p < 0.05), including p53, MAPK, and NAFLD signaling. Potential pairwise interactions between DE ncRNAs and mRNAs were fully characterized using in silico prediction and experimentally-validated evidence. We for the first time constructed a MLMI network of reciprocal interactions for 16 miRNAs, three lncRNAs, and 253 mRNAs in HCC. The predominant role of MEG3 in the MLMI network was validated by its overexpression in vitro that the expression levels of a proportion of MEG3-targeted miRNAs and mRNAs was changed significantly. Our results suggested that the comprehensive MLMI network synergistically modulated carcinogenesis, and the crosstalk of the network provides a new avenue to accurately describe the molecular mechanisms of hepatocarcinogenesis.

scholarly journals Analysis of a Preliminary microRNA Expression Signature in a Human Telangiectatic Osteogenic Sarcoma Cancer Cell Line

2021 ◽  
Vol 22 (3) ◽  
pp. 1163
Author(s):  
Gaia Palmini ◽  
Cecilia Romagnoli ◽  
Simone Donati ◽  
Roberto Zonefrati ◽  
Gianna Galli ◽  
...  
Keyword(s):  
Cell Line ◽  
Molecular Mechanisms ◽  
Osteogenic Sarcoma ◽  
Cancer Cell Line ◽  
Microscopic Features ◽  
In Vitro Establishment ◽  
Profile Characteristic ◽  
First Time

Telangiectatic osteosarcoma (TOS) is an aggressive variant of osteosarcoma (OS) with distinctive radiographic, gross, microscopic features, and prognostic implications. Despite several studies on OS, we are still far from understanding the molecular mechanisms of TOS. In recent years, many studies have demonstrated not only that microRNAs (miRNAs) are involved in OS tumorigenesis, development, and metastasis, but also that the presence in high-grade types of OS of cancer stem cells (CSCs) plays an important role in tumor progression. Despite these findings, nothing has been described previously about the expression of miRNAs and the presence of CSCs in human TOS. Therefore, we have isolated/characterized a putative CSC cell line from human TOS (TOS-CSCs) and evaluated the expression levels of several miRNAs in TOS-CSCs using real-time quantitative assays. We show, for the first time, the existence of CSCs in human TOS, highlighting the in vitro establishment of this unique stabilized cell line and an identification of a preliminary expression of the miRNA profile, characteristic of TOS-CSCs. These findings represent an important step in the study of the biology of one of the most aggressive variants of OS and the role of miRNAs in TOS-CSC behavior.

scholarly journals Role of Tumor Associated Fibroblasts in Human Liver Regeneration, Cirrhosis, and Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Daniela Cesselli ◽  
Antonio Paolo Beltrami ◽  
Alessandra Poz ◽  
Stefania Marzinotto ◽  
Elisa Comisso ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Human Liver ◽  
Adult Stem Cells ◽  
Experimental Studies ◽  
Tumor Cell Lines ◽  
Liver Scan ◽  
First Time

Tumor associated fibroblasts (TAFs) are considered a microenvironmental element critical for tumor growth and progression. Experimental studies suggest that their origin could be from mesenchymal stem cells (MSCs) derived from the bone marrow. However, the role played by TAFs in cirrhosis, hepatocellular carcinoma development, and progression is largely unknown, andin vitrohuman models are missing. This paper for the first time demonstrates that (1) human neoplastic livers possess a population of multipotent adult stem cells (MASCs) with properties of TAFs; (2) a population of MASC-derived TAFs is already present in cirrhotic, not yet neoplastic, livers; (3) MASCs isolated from nonneoplastic and noncirrhotic liver scan acquire a TAF phenotype when grown in a medium conditioned by tumor cell lines, supporting the notion that TAF could originate from resident primitive cells (MASCs), possibly through a paracrine mechanism.

scholarly journals Downregulation of CRABP2 Inhibit the Tumorigenesis of Hepatocellular Carcinoma In Vivo and In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Qingmin Chen ◽  
Ludong Tan ◽  
Zhe Jin ◽  
Yahui Liu ◽  
Ze Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retinoic Acid ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Hcc Cells

Cellular retinoic acid-binding protein 2 (CRABP2) binds retinoic acid (RA) in the cytoplasm and transports it into the nucleus, allowing for the regulation of specific downstream signal pathway. Abnormal expression of CRABP2 has been detected in the development of several tumors. However, the role of CRABP2 in hepatocellular carcinoma (HCC) has never been revealed. The current study aimed to investigate the role of CRABP2 in HCC and illuminate the potential molecular mechanisms. The expression of CRABP2 in HCC tissues and cell lines was detected by western blotting and immunohistochemistry assays. Our results demonstrated that the expression levels of CRABP2 in HCC tissues were elevated with the tumor stage development, and it was also elevated in HCC cell lines. To evaluate the function of CRABP2, shRNA-knockdown strategy was used in HCC cells. Cell proliferation, metastasis, and apoptosis were analyzed by CCK-8, EdU staining, transwell, and flow cytometry assays, respectively. Based on our results, knockdown of CRABP2 by shRNA resulted in the inhibition of tumor proliferation, migration, and invasion in vitro, followed by increased tumor apoptosis-related protein expression and decreased ERK/VEGF pathway-related proteins expression. CRABP2 silencing in HCC cells also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of CRABP2 in the development and development of HCC. Based on our findings, CRABP2 may be used as a novel diagnostic biomarker, and regulation of CRABP2 in HCC may provide a potential molecular target for the therapy of HCC.

scholarly journals Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma

Gut ◽  
2015 ◽  
Vol 66 (3) ◽  
pp. 530-540 ◽  
Author(s):  
Victoria Tovar ◽  
Helena Cornella ◽  
Agrin Moeini ◽  
Samuel Vidal ◽  
Yujin Hoshida ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Gene Signature ◽  
Signalling Pathways ◽  
Fgf Signalling

ObjectiveSorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterise the role of tumour-initiating cells (T-ICs) and signalling pathways involved in sorafenib resistance.DesignHCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: (1) role of T-ICs by in vitro sphere formation and in vivo tumourigenesis assays using NOD/SCID mice, (2) activation of alternative signalling pathways and (3) efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, quantitative real-time PCR (qRT-PCR)) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in two independent cohorts.ResultsSorafenib-acquired resistant tumours showed significant enrichment of T-ICs (164 cells needed to create a tumour) versus sorafenib-sensitive tumours (13 400 cells) and non-treated tumours (1292 cells), p<0.001. Tumours with sorafenib-acquired resistance were enriched with insulin-like growth factor (IGF) and fibroblast growth factor (FGF) signalling cascades (false discovery rate (FDR)<0.05). In vitro, cells derived from sorafenib-acquired resistant tumours and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumour growth and improved survival in sorafenib-resistant tumours. A sorafenib-resistance 175 gene signature was characterised by enrichment of progenitor cell features, aggressive tumorous traits and predicted poor survival in two cohorts (n=442 patients with HCC).ConclusionsAcquired resistance to sorafenib is driven by T-ICs with enrichment of progenitor markers and activation of IGF and FGF signalling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression.

scholarly journals The Role of Non-Coding RNAs in the Sorafenib Resistance of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinyao Hu ◽  
Hua Zhu ◽  
Yang Shen ◽  
Xiaoyu Zhang ◽  
Xiaoqin He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Circular Rnas ◽  
First Line ◽  
Advanced Hcc ◽  
Chemotherapy Agent ◽  
Development Of Resistance ◽  
Non Coding Rnas

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Sorafenib is approved by the U.S. Food and Drug Administration to be a first-line chemotherapy agent for patients with advanced HCC. A portion of advanced HCC patients can benefit from the treatment with sorafenib, but many patients ultimately develop sorafenib resistance, leading to a poor prognosis. The molecular mechanisms of sorafenib resistance are sophisticated and indefinite. Notably, non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are critically participated in the occurrence and progression of tumors. Moreover, growing evidence has suggested that ncRNAs are crucial regulators in the development of resistance to sorafenib. Herein, we integrally and systematically summarized the molecular mechanisms and vital role of ncRNAs impact sorafenib resistance of HCC, and ultimately explored the potential clinical administrations of ncRNAs as new prognostic biomarkers and therapeutic targets for HCC.

scholarly journals MAZ-LINC00645-GP73 Axis Promotes Hepatocellular Carcinoma Proliferation and Metastasis

2020 ◽  
Author(s):  
Yang Chen ◽  
Huiyan Li ◽  
Chunxun Liu ◽  
Yongmei Han ◽  
Yubao Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Tumor Promoter ◽  
Transcriptional Analysis ◽  
Luciferase Reporter ◽  
Chip Assay ◽  
Bioinformatics Analyses

Abstract BACKGROUND: Long non-coding RNAs (lncRNA) have been shown to play important roles in the development and progression of hepatocellular carcinoma (HCC). In this report, we examined the role of lncRNA LINC00645 in HCC. MATERIAL AND METHODS: Based on public databases and integrating bioinformatics analyses, the over-expression of LINC00645 in HCC tissues was detected and further validated in a cohort of liver tissues. A series of in vitro and in vivo functional experiments were executed to investigate the role of LINC00645 in the carcinogenesis and development of HCC. Comprehensive transcriptional analysis, chromatin immunoprecipitation (ChIP) assay, dual-luciferase reporter assay and western blot etc. were performed to explore the molecular mechanisms underlying the functions of LINC00645. RESULTS: LINC00645 was significantly upregulated in HCC cell lines and HCC tissues, which was correlated with poor prognosis in HCC patients. LINC00645 knockdown remarkably suppressed tumor growth in vitro and in vivo. Mechanistically, LINC00645 could competitively bind with miR-141-3p to prevent the degradation of its target gene GP73, which acts as a tumor-promoter in HCC. Furthermore, the ChIP assay showed that the transcription factor MAZ could bind to the LINC00645 promoter and increase its transcription. CONCLUSIONS: Collectively, this study demonstrated that LINC00645 plays a critical regulatory role in hepatocellular carcinoma cells and LINC00645 may serve as a potential diagnostic biomarker and therapeutic target of HCC. Thus, targeting MAZ/LINC00645/miR-141-3p/GP73 signaling axis may prevent the progression of HCC.

scholarly journals Pituitary Transcriptomic Study Reveals the Differential Regulation of lncRNAs and mRNAs Related to Prolificacy in Different FecB Genotyping Sheep

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 157 ◽  
Author(s):  
Jian Zheng ◽  
Zhibo Wang ◽  
Hua Yang ◽  
Xiaolei Yao ◽  
Pengcheng Yang ◽  
...  
Keyword(s):  
Litter Size ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Pituitary Cells ◽  
Rna Seq ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Hu Sheep

Long non-coding RNA (LncRNA) have been identified as important regulators in the hypothalamic-pituitary-ovarian axis associated with sheep prolificacy. However, their expression pattern and potential roles in the pituitary are yet unclear. To explore the potential mRNAs and lncRNAs that regulate the expression of the genes involved in sheep prolificacy, we used stranded specific RNA-seq to profile the pituitary transcriptome (lncRNA and mRNA) in high prolificacy (genotype FecB BB, litter size = 3; H) and low prolificacy sheep (genotype FecB B+; litter size = 1; L). Our results showed that 57 differentially expressed (DE) lncRNAs and 298 DE mRNAs were found in the pituitary between the two groups. The qRT-PCR results correlated well with the RNA-seq results. Moreover, functional annotation analysis showed that the target genes of the DE lncRNAs were significantly enriched in pituitary function, hormone-related pathways as well as response to stimulus and some other terms related to reproduction. Furthermore, a co-expression network of lncRNAs and target genes was constructed and reproduction related genes such as SMAD2, NMB and EFNB3 were included. Lastly, the interaction of candidate lncRNA MSTRG.259847.2 and its target gene SMAD2 were validated in vitro of sheep pituitary cells. These differential mRNA and lncRNA expression profiles provide a valuable resource for understanding the molecular mechanisms underlying Hu sheep prolificacy.

scholarly journals Coordinative control of G2/M phase of the cell cycle by non-coding RNAs in hepatocellular carcinoma

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5787 ◽  
Author(s):  
Jun Shi ◽  
Guangqiang Ye ◽  
Guoliang Zhao ◽  
Xuedong Wang ◽  
Chunhui Ye ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Target Genes ◽  
Expression Profiles ◽  
M Phase ◽  
Non Coding Rnas ◽  
Regulatory Model ◽  
Microarray Analyses ◽  
The Relationship

Objective To investigate the interaction of non-coding RNAs (ncRNAs) in hepatocellular carcinoma. Methods We compared the ncRNAs and mRNAs expression profiles of hepatocellular carcinoma and adjacent tissue by microarray and RT-PCR. The relationship between different ncRNAs and mRNA was analyzed using bioinformatics tools. A regulatory model of ncRNAs in hepatocellular carcinoma cells was developed. Results A total of 1,704 differentially expressed lncRNAs, 57 miRNAs, and 2,093 mRNAs were identified by microarray analyses. There is a co-expression relationship between two ncRNAs (miRNA-125b-2-3p and lncRNA P26302). Bioinformatics analysis demonstrated cyclin-dependent kinases 1 and CyclinA2 as potential targets of miR-125b-2-3p and Polo-like kinase 1 as potential target of lncRNAP26302. All three gene are important components in the G2/M phase of cell cycle. Subsequently real-time polymerase chain reaction (PCR) studies confirmed these microarray results. Conclusion MiR-125b-2-3p and lncRNAP26302 may affect the G2/M phase of the cell cycle through the regulation of their respective target genes. This study shows a role of ncRNAs in pathogenesis of hepatocellular carcinoma at molecular level, providing a basis for the future investigation aiming at early diagnosis and novel treatment of hepatocellular carcinoma.

scholarly journals RNA Network Interactions During Differentiation of Human Trophoblasts

2021 ◽  
Vol 9 ◽  
Author(s):  
Tianjiao Chu ◽  
Jean-Francois Mouillet ◽  
Zhishen Cao ◽  
Oren Barak ◽  
Yingshi Ouyang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Maternal Blood ◽  
Differentiation Process ◽  
Next Generation Sequencing Technology ◽  
Cell Layers ◽  
Capillary Endothelial Cells ◽  
Non Coding Rnas ◽  
Generation Sequencing

In the human placenta, two trophoblast cell layers separate the maternal blood from the villous basement membrane and fetal capillary endothelial cells. The inner layer, which is complete early in pregnancy and later becomes discontinuous, comprises the proliferative mononuclear cytotrophoblasts, which fuse together and differentiate to form the outer layer of multinucleated syncytiotrophoblasts. Because the syncytiotrophoblasts are responsible for key maternal-fetal exchange functions, tight regulation of this differentiation process is critical for the proper development and the functional role of the placenta. The molecular mechanisms regulating the fusion and differentiation of trophoblasts during human pregnancy remain poorly understood. To decipher the interactions of non-coding RNAs (ncRNAs) in this process, we exposed cultured primary human trophoblasts to standard in vitro differentiation conditions or to conditions known to hinder this differentiation process, namely exposure to hypoxia (O2 &lt; 1%) or to the addition of dimethyl sulfoxide (DMSO, 1.5%) to the culture medium. Using next generation sequencing technology, we analyzed the differential expression of trophoblastic lncRNAs, miRNAs, and mRNAs that are concordantly modulated by both hypoxia and DMSO. Additionally, we developed a model to construct a lncRNA-miRNA-mRNA co-expression network and inferred the functions of lncRNAs and miRNAs via indirect gene ontology analysis. This study improves our knowledge of the interactions between ncRNAs and mRNAs during trophoblast differentiation and identifies key biological processes that may be impaired in common gestational diseases, such as fetal growth restriction or preeclampsia.

Microarray to reveal LncRNA profile and the role of lncCUEDC1 in BCSCs.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 3-3
Author(s):  
Fengchun Zhang ◽  
Ying chun Xu ◽  
Ning Yan
Keyword(s):  
Breast Cancer ◽  
Cultured Cells ◽  
Bioinformatics Analyses ◽  
Functional Roles ◽  
Functional Activities ◽  
Non Coding Rnas ◽  
Microarray Analyses ◽  
First Time

3 Background: Recently, a growing amount of reports have shown that long non-coding RNAs (lncRNAs) are involved in breast cancer development, progression and metastasis. However, the correlation between lncRNAs and breast cancer stem cells (BCSCs) has been poorly explored. Methods: We initially isolated BCSCs from mammosphere-cultured cells; then, microarray analyses were carried out to detect the lncRNA signature in BCSCs. In addition, bioinformatics analyses, including Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), were consulted to explore the functional roles of lncRNAs on BCSCs. Results: A total of 142 aberrantly expressed lncRNAs in BCSCs were identified, and of those lncRNAs, 25 were downregulated and 117 were upregulated compared to non-BCSCs. In addition, some of these lncRNAs were randomly selected and verified by RT-PCR and sanger sequencing. Notably, bioinformatics data showed that the lncRNAs that were detected were largely associated with stemness-related signalling pathways. Additionally, an interacting network between lncRNAs and its mRNAs was constructed to further depict the lncRNA functional activities. Furthermore, we found that lncCUEDC1 negatively regulated phenotype and biological functions of BCSCs in vitro. Conclusions: Our work establishes the lncRNAs signature in BCSCs for the first time. These findings provide us with evidence to explore the functionalities of lncRNAs in BCSCs and indicate that lncCUED1 is a prospective target for BCSCs.

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