scholarly journals Identify and Validate the Transcriptomic, Functional Network, and Predictive Validity of FBXL19-AS1 in Hepatocellular Carcinoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Dingdong He ◽  
Xiaokang Zhang ◽  
Xinyu Zhu ◽  
Narayani Maharjan ◽  
Yingchao Wang ◽  
...  

Hepatocellular carcinoma (HCC) is one of the most common neoplastic diseases worldwide. Available biomarkers are not sensitive enough for the diagnosis of HCC, hence seeking new biomarkers of HCC is urgent and challenging. The purpose of this study was to investigate the role of F-box and leucine-rich repeat protein 19-antisense RNA 1 (FBXL19-AS1) through a functional network and inquire into its diagnostic and prognostic value in HCC. A comprehensive strategy of genomic data mining, bioinformatics and experimental validation was used to evaluate the clinical value of FBXL19-AS1 in the diagnosis and prognosis of HCC and to identify the pathways in which FBXL19-AS1 might be involved. FBXL19-AS1 was up-regulated in HCC tissues, and its high expression was associated with TNM stage and poor prognosis of HCC patients. The combination of FBXL19-AS1 and alpha-fetoprotein (AFP) in plasma could prominently improve the diagnostic validity for HCC. FBXL19-AS1 might stabilize FBXL19 to reduce the amount of macrophage M1, and then promote the occurrence and development of HCC. Meanwhile, FBXL19-AS1 might participate in regulating HCC related pathways through FBXL19-AS1-miRNA-mRNA network. Our findings indicated that FBXL19-AS1 not only serves as a potential biomarker for HCC diagnosis and prognosis, but also might be functionally carcinogenic.

Author(s):  
Dingdong He ◽  
Xiaokang Zhang ◽  
Xinyu Zhu ◽  
Narayani Maharjan ◽  
Yingchao Wang ◽  
...  

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common neoplastic diseases worldwide. Available biomarkers are not sensitive enough for the diagnosis of HCC, seeking new biomarkers of HCC is urgent and challenging. The purpose of this study was to investigate the role of F-box and leucine-rich repeat protein 19-antisense RNA 1 (FBXL19-AS1) through competing endogenous RNA (ceRNA) network and its diagnostic and prognostic value in HCC.Methods: A comprehensive strategy of genomic data mining, bioinformatics and experimental validation was used to evaluate the clinical value of FBXL19-AS1 in the diagnosis and prognosis of HCC and to identify the pathways that FBXL19-AS1 may be involved in.Results: FBXL19-AS1 was up-regulated in HCC, and its high expression was associated with TNM stage and poor prognosis of HCC patients. The combined use of plasma FBXL19-AS1 and alpha-fetoprotein (AFP) could prominently improve the diagnostic validity for HCC. FBXL19-AS1 might participate in regulating HCC related pathways, including hepatitis C, hepatitis B, microRNAs in cancer, cell cycle, viral carcinogenesis, and proteoglycans in cancer through ceRNA network.Conclusions: Our findings indicated that FBXL19-AS1 not only serves as a potential biomarker for HCC diagnosis and prognosis, but it may be functionally carcinogenic.


Epigenomics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1209-1231 ◽  
Author(s):  
Xin-Liang Ming ◽  
Yan-Lin Feng ◽  
Ding-Dong He ◽  
Chang-Liang Luo ◽  
Jia-Ling Rong ◽  
...  

Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results: BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA–miRNA–mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.


2020 ◽  
Vol 48 (5) ◽  
pp. 2295-2305
Author(s):  
Jiawei Zhang ◽  
Dandan Li ◽  
Rui Zhang ◽  
Peng Gao ◽  
Rongxue Peng ◽  
...  

The role of miR-21 in the pathogenesis of various liver diseases, together with the possibility of detecting microRNA in the circulation, makes miR-21 a potential biomarker for noninvasive detection. In this review, we summarize the potential utility of extracellular miR-21 in the clinical management of hepatic disease patients and compared it with the current clinical practice. MiR-21 shows screening and prognostic value for liver cancer. In liver cirrhosis, miR-21 may serve as a biomarker for the differentiating diagnosis and prognosis. MiR-21 is also a potential biomarker for the severity of hepatitis. We elucidate the disease condition under which miR-21 testing can reach the expected performance. Though miR-21 is a key regulator of liver diseases, microRNAs coordinate with each other in the complex regulatory network. As a result, the performance of miR-21 is better when combined with other microRNAs or classical biomarkers under certain clinical circumstances.


2021 ◽  
Vol 11 (3) ◽  
pp. 219
Author(s):  
Ya-Ling Yang ◽  
Yen-Hsiang Chang ◽  
Chia-Jung Li ◽  
Ying-Hsien Huang ◽  
Ming-Chao Tsai ◽  
...  

Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guolin Chen ◽  
Wei Zhang ◽  
Yiran Ben

Background: Hepatitis C virus (HCV) infection is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Despite recent advances in the understanding of the biological basis of HCC development, the molecular mechanisms underlying HCV-induced HCC (HCC-HCV) remain unclear. The carcinogenic potential of HCV varies according to the genotype and mutation in its viral sequence. Moreover, regulatory pathways play important roles in many pathogenic processes. Therefore, identifying the pathways by which HCV induces HCC may enable improved HCC diagnosis and treatment.Methods: We employed a systematic approach to identify an important regulatory module in the process of HCV-HCC development to find the important regulators. First, an HCV-related HCC subnetwork was constructed based on the gene expression in HCC-HCV patients and HCC patients. A priority algorithm was then used to extract the module from the subnetworks, and all the regulatory relationships of the core genes of the network were extracted. Integrating the significantly highly mutated genes involved in the HCC-HCV patients, core regulatory modules and key regulators related to disease prognosis and progression were identified.Result: The key regulatory genes including EXO1, VCAN, KIT, and hsa-miR-200c-5p were found to play vital roles in HCV-HCC development. Based on the statistics analysis, EXO1, VCAN, and KIT mutations are potential biomarkers for HCV–HCC prognosis at the genomic level, whereas has-miR-200c-5P is a potential biomarker for HCV–HCC prognosis at the expression level.Conclusion: We identified three significantly mutated genes and one differentially expressed miRNA, all related to HCC prognosis. As potential pathogenic factors of HCC, these genes and the miRNA could be new biomarkers for HCV-HCC diagnosis.


2020 ◽  
Author(s):  
Malihe Bagheri ◽  
Behzad Khansarinejad ◽  
Ghasem Mosayebi ◽  
Alireza Moradabadi ◽  
Mahdieh Mondanizadeh

Abstract Background: Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancy in adults worldwide. This cancer has a poor prognosis at different stages. So, the identification of new biomarkers is important for early diagnosis of B-CLL. Considering the oncogenic role of APRIL molecule in this leukemia as well as the regulatory role of microRNAs (miRNAs) in different signaling pathways, the present study evaluated the miRNAs targeting APRIL gene in B-CLL.Methods: The miRNAs were predicted and selected using bioinformatics algorithms. A total of 80 plasma samples (40 samples of healthy individuals and 40 samples of B-CLL patients) were subjected to RNA extraction and synthesis of cDNA. The expressions levels of predicted miRNAs and APRIL gene in plasma of B-CLL patients and healthy individuals were assessed by Real time PCR analysis. ROC analysis was performed to investigate the role predicted miRNAs as novel biomarkers in diagnosis of B-CLL. Results: The results of the prediction showed that miR-145-5p and miR-185-5p target the APRIL gene. The expression level of APRIL gene was strikingly higher in plasma of B-CLL patients than in the healthy individuals (102, P= 0.001). On the other hand, expression levels of miR-145-5p and miR-185-5p were strikingly lower in B-CLL patients than in the healthy individuals (0.07, P= 0.001) (0.29, P= 0.001). Also, ROC curve analyses demonstrated that miR-145-5p and miR-185-5p are specific and sensitive and may serve as new biomarkers for the early detection of B-CLL. Conclusions: These data suggest that the study miRNAs may have a role in B-CLL development and progression. Moreover, miR-145-5p and miR-185-5p can be served as a novel and potential biomarker in the diagnosis of B-CLL.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Luca Faloppi ◽  
Maristella Bianconi ◽  
Riccardo Memeo ◽  
Andrea Casadei Gardini ◽  
Riccardo Giampieri ◽  
...  

Hepatocellular carcinoma (HCC) is the most common primary liver tumour (80–90%) and represents more than 5.7% of all cancers. Although in recent years the therapeutic options for these patients have increased, clinical results are yet unsatisfactory and the prognosis remains dismal. Clinical or molecular criteria allowing a more accurate selection of patients are in fact largely lacking. Lactic dehydrogenase (LDH) is a glycolytic key enzyme in the conversion of pyruvate to lactate under anaerobic conditions. In preclinical models, upregulation of LDH has been suggested to ensure both an efficient anaerobic/glycolytic metabolism and a reduced dependence on oxygen under hypoxic conditions in tumour cells. Data from several analyses on different tumour types seem to suggest that LDH levels may be a significant prognostic factor. The role of LDH in HCC has been investigated by different authors in heterogeneous populations of patients. It has been tested as a potential biomarker in retrospective, small, and nonfocused studies in patients undergoing surgery, transarterial chemoembolization (TACE), and systemic therapy. In the major part of these studies, high LDH serum levels seem to predict a poorer outcome. We have reviewed literature in this setting trying to resume basis for future studies validating the role of LDH in this disease.


2021 ◽  
Author(s):  
Maria Elizbeth Alvarez-Sanchez ◽  
Oscar Rojas Espinosa ◽  
Julio César Torres-Romero ◽  
Ereth Ameyatzin Robles Chávez ◽  
Edgar Estrella-Parra ◽  
...  

Over the past two decades, several research groups have focused on the functioning of microRNAs (miRNAs), because many of them function as positive or negative endogenous regulators of processes that alter during the development of cancer. Prostate cancer is the second most commonly occurring cancer in men. New biomarkers are needed to support the diagnosis of prostate cancer. Although it is necessary to deepen the research on this molecule to explore its potential utility in the diagnosis, follow-up, and prognosis of cancer, our results support a role of miR-107 in the signaling cascades that allow cancer progression, and as shown here, in the progression of Prostate Cancer (PCa). These findings strongly suggest that miR-107 may be a potential circulating biomarker for the diagnosis and prognosis of prostate cancer.


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