scholarly journals MicroRNAs in Hepatocellular Carcinoma: Regulation, Function, and Clinical Implications

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Jie Sun ◽  
Haiqi Lu ◽  
Xian Wang ◽  
Hongchuan Jin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor Genes ◽  
Early Stage ◽  
Untranslated Regions ◽  
Clinical Implications ◽  
Messenger Rnas ◽  
Aberrant Expression ◽  
Regulate Gene Expression ◽  
Poor Understanding ◽  
Regulation Function

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related death. Poor understanding of the mechanisms underlying the pathogenesis of HCC makes it difficult to be diagnosed and treated at early stage. MicroRNAs (miRNAs), a class of noncoding single-stranded RNAs of ~22 nucleotides in length, posttranscriptionally regulate gene expression by base pairing with the3′untranslated regions (3′UTRs) of target messenger RNAs (mRNAs). Aberrant expression of miRNAs is found in many if not all cancers, and many deregulated miRNAs have been proved to play crucial roles in the initiation and progression of cancers by regulating the expression of various oncogenes or tumor suppressor genes. In this Paper, we will summarize the regulations and functions of miRNAs aberrantly expressed in HCC and discuss the potential application of miRNAs as diagnostic and prognostic biomarkers of HCC and their potential roles in the intervention of HCC.

scholarly journals An RNA–RNA crosstalk network involving HMGB1 and RICTOR facilitates hepatocellular carcinoma tumorigenesis by promoting glutamine metabolism and impedes immunotherapy by PD-L1+ exosomes activity

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yanping Wei ◽  
Xuewu Tang ◽  
Yibin Ren ◽  
Yun Yang ◽  
Fengliang Song ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Feedback Loop ◽  
Early Stage ◽  
Glutamine Metabolism ◽  
Untranslated Regions ◽  
Mtorc1 Signaling ◽  
Precision Therapy ◽  
Competing Endogenous Rnas ◽  
Hcc Cells

AbstractHepatocellular carcinoma (HCC) is the global leading cause of cancer-related deaths due to the deficiency of targets for precision therapy. A new modality of epigenetic regulation has emerged involving RNA–RNA crosstalk networks where two or more competing endogenous RNAs (ceRNAs) bind to the same microRNAs. However, the contribution of such mechanisms in HCC has not been well studied. Herein, potential HMGB1-driven RNA–RNA crosstalk networks were evaluated at different HCC stages, identifying the mTORC2 component RICTOR as a potential HMGB1 ceRNA in HBV+ early stage HCC. Indeed, elevated HMGB1 mRNA was found to promote the expression of RICTOR mRNA through competitively binding with the miR-200 family, especially miR-429. Functional assays employing overexpression or interference strategies demonstrated that the HMGB1 and RICTOR 3′untranslated regions (UTR) epigenetically promoted the malignant proliferation, self-renewal, and tumorigenesis in HCC cells. Intriguingly, interference against HMGB1 and RICTOR in HCC cells promoted a stronger anti-PD-L1 immunotherapy response, which appeared to associate with the production of PD-L1+ exosomes. Mechanistically, the HMGB1-driven RNA-RNA crosstalk network facilitated HCC cell glutamine metabolism via dual mechanisms, activating a positive feedback loop involving mTORC2-AKT-C-MYC to upregulate glutamine synthetase (GS) expression, and inducing mTORC1 signaling to derepress SIRT4 on glutamate dehydrogenase (GDH). Meanwhile, this crosstalk network could impede the efficacy of immunotherapy through mTORC1-P70S6K dependent PD-L1 production and PD-L1+ exosomes activity. In conclusion, our study highlights the non-coding regulatory role of HMGB1 with implications for RNA-based therapeutic targeting together with a prediction of anti-PD-L1 immunotherapy in HCC.

scholarly journals The Regulatory Role of MicroRNAs in Breast Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4940 ◽  
Author(s):  
Hui-Yi Loh ◽  
Brendan P. Norman ◽  
Kok-Song Lai ◽  
Nik Mohd Afizan Nik Abd. Rahman ◽  
Noorjahan Banu Mohamed Alitheen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Recurrence ◽  
Messenger Rnas ◽  
Aberrant Expression ◽  
Regulate Gene Expression ◽  
Rna Molecules ◽  
Current State ◽  
Non Coding Rna ◽  
State Of Research

MicroRNAs (miRNAs) are small non-coding RNA molecules which function as critical post-transcriptional gene regulators of various biological functions. Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs (mRNAs), thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. Different cellular pathways of breast cancer development such as cell proliferation, apoptotic response, metastasis, cancer recurrence and chemoresistance are regulated by either the oncogenic miRNA (oncomiR) or tumor suppressor miRNA (tsmiR). In this review, we highlight the current state of research into miRNA involved in breast cancer, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus. The post-transcriptional gene regulatory roles of various dysregulated miRNAs in breast cancer and their potential as therapeutic targets are also discussed.

scholarly journals MicroRNA Expression in Selected Carcinomas of the Gastrointestinal Tract

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Nicole C. Panarelli ◽  
Rhonda K. Yantiss
Keyword(s):  
Gastrointestinal Tract ◽  
Mirna Expression ◽  
Tumor Suppressor Genes ◽  
Noncoding Rna ◽  
Messenger Rnas ◽  
Rna Sequences ◽  
Regulate Gene Expression ◽  
Number Of Genes ◽  
Mirna Species ◽  
Posttranscriptional Level

MicroRNAs (miRNAs) comprise a recently discovered class of small, 18–25 nucleotide, noncoding RNA sequences that regulate gene expression at the posttranscriptional level by binding to and inhibiting the translation of target messenger RNAs (mRNAs). Characteristic patterns of miRNA expression have been described in several malignancies of the gastrointestinal tract, and numerous investigators have demonstrated interactions between specific miRNA species and target oncogenes or tumor-suppressor genes. It is clear that miRNAs play an important role in regulating expression of a number of genes involved in gastrointestinal carcinogenesis, and, thus, these molecules may represent either diagnostic markers of, or therapeutic targets for, some types of malignancy. This paper summarizes the literature regarding miRNA expression in carcinomas of the colon, pancreas, and liver and discusses some of the mechanisms by which these molecules participate in gastrointestinal oncogenesis.

scholarly journals Bacterial 3′UTRs: A Useful Resource in Post-transcriptional Regulation

2021 ◽  
Vol 7 ◽  
Author(s):  
Pilar Menendez-Gil ◽  
Alejandro Toledo-Arana
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Untranslated Regions ◽  
Messenger Rnas ◽  
Specific Expression ◽  
Regulate Gene Expression ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms ◽  
Species Specific ◽  
Post Transcriptional Regulation

Bacterial messenger RNAs (mRNAs) are composed of 5′ and 3′ untranslated regions (UTRs) that flank the coding sequences (CDSs). In eukaryotes, 3′UTRs play key roles in post-transcriptional regulatory mechanisms. Shortening or deregulation of these regions is associated with diseases such as cancer and metabolic disorders. Comparatively, little is known about the functions of 3′UTRs in bacteria. Over the past few years, 3′UTRs have emerged as important players in the regulation of relevant bacterial processes such as virulence, iron metabolism, and biofilm formation. This MiniReview is an update for the different 3′UTR-mediated mechanisms that regulate gene expression in bacteria. Some of these include 3′UTRs that interact with the 5′UTR of the same transcript to modulate translation, 3′UTRs that are targeted by specific ribonucleases, RNA-binding proteins and small RNAs (sRNAs), and 3′UTRs that act as reservoirs of trans-acting sRNAs, among others. In addition, recent findings regarding a differential evolution of bacterial 3′UTRs and its impact in the species-specific expression of orthologous genes are also discussed.

Wisp1 as an early stage marker of human hepatocellular carcinoma (HCC)?

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
A Dropmann ◽  
T Feng ◽  
T Dediulia ◽  
I Ilkavets ◽  
B Hofmann ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
Human Hepatocellular Carcinoma

miR-224 is an early-stage biomarker of hepatocellular carcinoma with miR-224 and miR-125b as prognostic biomarkers

2020 ◽  
Vol 14 (15) ◽  
pp. 1485-1500
Author(s):  
Lichao Yang ◽  
Chunmeng Wei ◽  
Yasi Li ◽  
Xiao He ◽  
Min He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Survival Analysis ◽  
Sensitivity And Specificity ◽  
Poor Prognosis ◽  
Early Stage ◽  
Meta Analysis ◽  
Benign Lesion ◽  
Diagnostic Efficiency ◽  
Low Expression

Aim: The aim was to systematically investigate the miRNA biomarkers for early diagnosis of hepatocellular carcinoma (HCC). Materials & methods: A systematic review and meta-analysis of miRNA expression in HCC were performed. Results: A total of 4903 cases from 30 original studies were comprehensively analyzed. The sensitivity and specificity of miR-224 in discriminating early-stage HCC patients from benign lesion patients were 0.868 and 0.792, which were superior to α-fetoprotein. Combined miR-224 with α-fetoprotein, the sensitivity and specificity were increased to 0.882 and 0.808. Prognostic survival analysis showed low expression of miR-125b and high expression of miR-224 were associated with poor prognosis. Conclusion: miR-224 had a prominent diagnostic efficiency in early-stage HCC, with miR-224 and miR-125b being valuable in the prognostic diagnosis.

scholarly journals The Treatment Effect of Liver Transplantation versus Liver Resection for HCC: A Review and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3730
Author(s):  
Berend R. Beumer ◽  
Roeland F. de Wilde ◽  
Herold J. Metselaar ◽  
Robert A. de Man ◽  
Wojciech G. Polak ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Resection ◽  
Early Stage ◽  
Disease Free Survival ◽  
Milan Criteria ◽  
Term Survival ◽  
Equal Distribution ◽  
Intention To Treat ◽  
Treat Analysis

For patients presenting with hepatocellular carcinoma within the Milan criteria, either liver resection or liver transplantation can be performed. However, to what extent either of these treatment options is superior in terms of long-term survival is unknown. Obviously, the comparison of these treatments is complicated by several selection processes. In this article, we comprehensively review the current literature with a focus on factors accounting for selection bias. Thus far, studies that did not perform an intention-to-treat analysis conclude that liver transplantation is superior to liver resection for early-stage hepatocellular carcinoma. In contrast, studies performing an intention-to-treat analysis state that survival is comparable between both modalities. Furthermore, all studies demonstrate that disease-free survival is longer after liver transplantation compared to liver resection. With respect to the latter, implications of recurrences for survival are rarely discussed. Heterogeneous treatment effects and logical inconsistencies indicate that studies with a higher level of evidence are needed to determine if liver transplantation offers a survival benefit over liver resection. However, randomised controlled trials, as the golden standard, are believed to be infeasible. Therefore, we suggest an alternative research design from the causal inference literature. The rationale for a regression discontinuity design that exploits the natural experiment created by the widely adopted Milan criteria will be discussed. In this type of study, the analysis is focused on liver transplantation patients just within the Milan criteria and liver resection patients just outside, hereby ensuring equal distribution of confounders.

scholarly journals The APAC Score: A Novel and Highly Performant Serological Tool for Early Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

2021 ◽  
Vol 10 (15) ◽  
pp. 3392
Author(s):  
Joeri Lambrecht ◽  
Mustafa Porsch-Özçürümez ◽  
Jan Best ◽  
Fabian Jost-Brinkmann ◽  
Christoph Roderburg ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
At Risk ◽  
Liver Cirrhosis ◽  
Early Stage ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Serum Samples ◽  
Disease Etiology ◽  
Risk Patients ◽  
Scoring Tool

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.

scholarly journals Identification of BHLHE40 expression in peripheral blood mononuclear cells as a novel biomarker for diagnosis and prognosis of hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pattapon Kunadirek ◽  
Chaiyaboot Ariyachet ◽  
Supachaya Sriphoosanaphan ◽  
Nutcha Pinjaroen ◽  
Pongserath Sirichindakul ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Early Stage ◽  
High Sensitivity ◽  
Peripheral Blood Mononuclear ◽  
Diagnosis And Prognosis ◽  
Transcription Profiles ◽  
Blood Mononuclear Cells

AbstractNovel and sensitive biomarkers is highly required for early detection and predicting prognosis of hepatocellular carcinoma (HCC). Here, we investigated transcription profiles from peripheral blood mononuclear cells (PBMCs) of 8 patients with HCC and PBMCs from co-culture model with HCC using RNA-Sequencing. These transcription profiles were cross compared with published microarray datasets of PBMCs in HCC to identify differentially expressed genes (DEGs). A total of commonly identified of 24 DEGs among these data were proposed as cancer-induced genes in PBMCs, including 18 upregulated and 6 downregulated DEGs. The KEGG pathway showed that these enriched genes were mainly associated with immune responses. Five up-regulated candidate genes including BHLHE40, AREG, SOCS1, CCL5, and DDIT4 were selected and further validated in PBMCs of 100 patients with HBV-related HCC, 100 patients with chronic HBV infection and 100 healthy controls. Based on ROC analysis, BHLHE40 and DDIT4 displayed better diagnostic performance than alpha-fetoprotein (AFP) in discriminating HCC from controls. Additionally, BHLHE40 and DDIT4 had high sensitivity for detecting AFP-negative and early-stage HCC. BHLHE40 was also emerged as an independent prognostic factor of overall survival of HCC. Together, our study indicated that BHLHE40 in PBMCs could be a promising diagnostic and prognostic biomarker for HBV-related HCC.

Sign in / Sign up

Export Citation Format

Share Document