scholarly journals Molecular and Functional Roles of MicroRNAs in the Progression of Hepatocellular Carcinoma—A Review

2020 ◽  
Vol 21 (21) ◽  
pp. 8362
Author(s):  
Kyoko Oura ◽  
Asahiro Morishita ◽  
Tsutomu Masaki
Keyword(s):  
Hepatocellular Carcinoma ◽  
Control Cell ◽  
Messenger Rnas ◽  
Functional Roles ◽  
Multiple Risk Factors ◽  
Biological Phenomena ◽  
Viral Hepatitis B ◽  
Novel Biomarkers ◽  
Non Coding Rnas ◽  
Made In

Liver cancer is the fourth leading cause of cancer deaths globally, of which hepatocellular carcinoma (HCC) is the major subtype. Viral hepatitis B and C infections, alcohol abuse, and metabolic disorders are multiple risk factors for liver cirrhosis and HCC development. Although great therapeutic advances have been made in recent decades, the prognosis for HCC patients remains poor due to late diagnosis, chemotherapy failure, and frequent recurrence. MicroRNAs (miRNAs) are endogenous, non-coding RNAs that regulate various molecular biological phenomena by suppressing the translation of target messenger RNAs (mRNAs). miRNAs, which often become dysregulated in malignancy, control cell proliferation, migration, invasion, and development in HCC by promoting or suppressing tumors. Exploring the detailed mechanisms underlying miRNA-mediated HCC development and progression can likely improve the outcomes of patients with HCC. This review summarizes the molecular and functional roles of miRNAs in the pathogenesis of HCC. Further, it elucidates the utility of miRNAs as novel biomarkers and therapeutic targets.

scholarly journals Extracellular Vesicle Associated Non-Coding RNAs in Lung Infections and Injury

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 965
Author(s):  
Zhi Hao Kwok ◽  
Kareemah Ni ◽  
Yang Jin
Keyword(s):  
Extracellular Vesicle ◽  
Human Diseases ◽  
Future Research ◽  
Functional Roles ◽  
Bodily Fluids ◽  
Wide Range ◽  
Novel Biomarkers ◽  
Heterogenous Population ◽  
Non Coding Rnas ◽  
Functional Relevance

Extracellular vesicles (EVs) refer to a heterogenous population of membrane-bound vesicles that are released by cells under physiological and pathological conditions. The detection of EVs in the majority of the bodily fluids, coupled with their diverse cargo comprising of DNA, RNA, lipids, and proteins, have led to the accumulated interests in leveraging these nanoparticles for diagnostic and therapeutic purposes. In particular, emerging studies have identified enhanced levels of a wide range of specific subclasses of non-coding RNAs (ncRNAs) in EVs, thereby suggesting the existence of highly selective and regulated molecular processes governing the sorting of these RNAs into EVs. Recent studies have also illustrated the functional relevance of these enriched ncRNAs in a variety of human diseases. This review summarizes the current state of knowledge on EV-ncRNAs, as well as their functions and significance in lung infection and injury. As a majority of the studies on EV-ncRNAs in lung diseases have focused on EV-microRNAs, we will particularly highlight the relevance of these molecules in the pathophysiology of these conditions, as well as their potential as novel biomarkers therein. We also outline the current challenges in the EV field amidst the tremendous efforts to propel the clinical utility of EVs for human diseases. The lack of published literature on the functional roles of other EV-ncRNA subtypes may in turn provide new avenues for future research to exploit their feasibility as novel diagnostic and therapeutic targets in human diseases.

scholarly journals HULC and Linc00152 Act as Novel Biomarkers in Predicting Diagnosis of Hepatocellular Carcinoma

2015 ◽  
Vol 37 (2) ◽  
pp. 687-696 ◽  
Author(s):  
Jun Li ◽  
Xiaochen Wang ◽  
Junwei Tang ◽  
Runqiu Jiang ◽  
Wenjie Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Operating Characteristic ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Double Blind ◽  
Novel Biomarkers ◽  
Non Coding Rnas ◽  
Validation Set ◽  
And Control ◽  
Tissues Expression

Background/Aims: The alterations of long non-coding RNAs (lncRNAs) are related to multiple diseases. They can be detected in plasma as biomarkers for the diagnosis of multiple diseases. In this study, we aimed to determine the expression of circulating lncRNAs in human, which may be promising biomarkers for the diagnosis of hepatocellular carcinoma (HCC). Methods: Eight lncRNAs were chosen as candidates on the basis of the literature to evaluate the diagnostic value and accuracy of the plasma lncRNA profiling system. The candidate lncRNAs were validated by qRT-PCR arranged in the training and validation sets. Additional double-blind testing was performed in 20 patients clinically suspected of having HCC. Results: Circulating HULC and Linc00152 were significantly up-regulated in plasma samples of HCC patients during training set and validation set. Areas under the receiver operating characteristic (ROC) curves of the validated two lncRNAs signature were 0.78 and 0.85, respectively. Combination of HULC and Linc00152 possessed a moderate ability to discrimination between HCC and control with an area under ROC value of 0.87 while the combination of AFP was 0.89 with a positive correlation with tissues expression. Conclusions: Our results suggest that both plasma levels of HULC and Linc00152 achieve a fine diagnostic accuracy in diagnosing ontogenesis and metastasis of HCC and may act as novel biomarkers for HCC.

scholarly journals Identification and targeting of G-quadruplex structures in MALAT1 long non-coding RNA

2021 ◽  
Author(s):  
Xi Mou ◽  
Shiau Wei Liew ◽  
Chun Kit Kwok
Keyword(s):  
High Specificity ◽  
Messenger Rnas ◽  
Functional Roles ◽  
Cellular Processes ◽  
Multiple Strategies ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Nuclear Cell

RNA G-quadruplexes (rG4s) have functional roles in many cellular processes in diverse organisms. While a number of rG4 examples have been reported in coding messenger RNAs (mRNA), so far only limited works have studied rG4s in non-coding RNAs (ncRNAs), especially in long non-coding RNAs (lncRNAs) that are of emerging interest and significance in biology. Herein, we report that MALAT1 lncRNA contains conserved rG4 motifs, forming thermostable rG4 structures with parallel topology. We also show that rG4s in MALAT1 lncRNA can interact with NONO protein with high specificity and affinity in vitro and in nuclear cell lysate, and we provide in vivo data to support that NONO protein recognizes MALAT1 lncRNA via rG4 motifs. Notably, we demonstrate that rG4s in MALAT1 lncRNA can be targeted by rG4-specific small molecule, peptide, and L-aptamer, leading to the dissociation of MALAT1 rG4-NONO protein interaction. Altogether, this study uncovers new and important rG4s in MALAT1 lncRNAs, reveals their specific interactions with NONO protein, offers multiple strategies for targeting MALAT1 and its RNA-protein complex via its rG4 structure, and illustrates the prevalence and significance of rG4s in ncRNAs.

MicroRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma

2019 ◽  
Vol 20 (11) ◽  
pp. 1129-1140 ◽  
Author(s):  
Seyed Mostafa Parizadeh ◽  
Reza Jafarzadeh-Esfehani ◽  
Maryam Ghandehari ◽  
Fatemeh Goldani ◽  
Seyed Mohammad Reza Parizadeh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Diagnosis ◽  
Biological Activities ◽  
Radical Resection ◽  
High Rate ◽  
Average Survival ◽  
Specific Tumor ◽  
Serum Alpha Fetoprotein ◽  
Novel Biomarkers ◽  
Patients Experience

Hepatocellular carcinoma (HCC) is a common cancer, and the second most common cause of cancer-associated death globally. One of the major reasons for this high rate of mortality is a failure to make an early diagnosis. The average survival in untreated HCC patients is estimated to be approximately three months. The 5-year overall survival rate after radical resection is about 15-40% and within two years, more than two third of patients experience a relapse. To date, the most common biomarker which has been used for the diagnosis of HCC is serum alpha-fetoprotein (AFP). However, there is a lack of sensitive and specific tumor biomarkers for the early diagnosis of HCC. MicroRNAs are a class of short endogenous RNA with crucial role in many biological activities and cellular pathways and can be found in various tissues and body fluids. The aim of this review was to summarize the results of recent studies investigating miRNAs as novel biomarkers for the early diagnosis and prognostic risk stratification of patients with this type of liver cancer.

scholarly journals Inosine in Biology and Disease

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 600
Author(s):  
Sundaramoorthy Srinivasan ◽  
Adrian Gabriel Torres ◽  
Lluís Ribas de Pouplana
Keyword(s):  
Human Health ◽  
Purine Biosynthesis ◽  
Messenger Rnas ◽  
Transfer Rnas ◽  
Functional Roles ◽  
Codon Recognition ◽  
Wobble Position ◽  
Biosynthesis Gene ◽  
The Stability ◽  
Cell Signaling Pathways

The nucleoside inosine plays an important role in purine biosynthesis, gene translation, and modulation of the fate of RNAs. The editing of adenosine to inosine is a widespread post-transcriptional modification in transfer RNAs (tRNAs) and messenger RNAs (mRNAs). At the wobble position of tRNA anticodons, inosine profoundly modifies codon recognition, while in mRNA, inosines can modify the sequence of the translated polypeptide or modulate the stability, localization, and splicing of transcripts. Inosine is also found in non-coding and exogenous RNAs, where it plays key structural and functional roles. In addition, molecular inosine is an important secondary metabolite in purine metabolism that also acts as a molecular messenger in cell signaling pathways. Here, we review the functional roles of inosine in biology and their connections to human health.

scholarly journals Investigation of long non-coding RNAs as regulatory players of grapevine response to powdery and downy mildew infection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Garima Bhatia ◽  
Santosh K. Upadhyay ◽  
Anuradha Upadhyay ◽  
Kashmir Singh
Keyword(s):  
Downy Mildew ◽  
Plasmopara Viticola ◽  
Defense Responses ◽  
Protein Coding ◽  
Functional Roles ◽  
Real Time Quantitative Pcr ◽  
Transcriptional Reprogramming ◽  
Sequencing Technologies ◽  
Non Coding Rnas ◽  
Fungal Phytopathogens

Abstract Background Long non-coding RNAs (lncRNAs) are regulatory transcripts of length > 200 nt. Owing to the rapidly progressing RNA-sequencing technologies, lncRNAs are emerging as considerable nodes in the plant antifungal defense networks. Therefore, we investigated their role in Vitis vinifera (grapevine) in response to obligate biotrophic fungal phytopathogens, Erysiphe necator (powdery mildew, PM) and Plasmopara viticola (downy mildew, DM), which impose huge agro-economic burden on grape-growers worldwide. Results Using computational approach based on RNA-seq data, 71 PM- and 83 DM-responsive V. vinifera lncRNAs were identified and comprehensively examined for their putative functional roles in plant defense response. V. vinifera protein coding sequences (CDS) were also profiled based on expression levels, and 1037 PM-responsive and 670 DM-responsive CDS were identified. Next, co-expression analysis-based functional annotation revealed their association with gene ontology (GO) terms for ‘response to stress’, ‘response to biotic stimulus’, ‘immune system process’, etc. Further investigation based on analysis of domains, enzyme classification, pathways enrichment, transcription factors (TFs), interactions with microRNAs (miRNAs), and real-time quantitative PCR of lncRNAs and co-expressing CDS pairs suggested their involvement in modulation of basal and specific defense responses such as: Ca2+-dependent signaling, cell wall reinforcement, reactive oxygen species metabolism, pathogenesis related proteins accumulation, phytohormonal signal transduction, and secondary metabolism. Conclusions Overall, the identified lncRNAs provide insights into the underlying intricacy of grapevine transcriptional reprogramming/post-transcriptional regulation to delay or seize the living cell-dependent pathogen growth. Therefore, in addition to defense-responsive genes such as TFs, the identified lncRNAs can be further examined and leveraged to candidates for biotechnological improvement/breeding to enhance fungal stress resistance in this susceptible fruit crop of economic and nutritional importance.

scholarly journals Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Haoting Sun ◽  
Chaoqun Wang ◽  
Beiyuan Hu ◽  
Xiaomei Gao ◽  
Tiantian Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Calcium Binding ◽  
Tumor Metastasis ◽  
Metastatic Potential ◽  
Functional Roles ◽  
Stat3 Phosphorylation ◽  
Hcc Cells

AbstractIntercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

scholarly journals Roles of ncRNAs as ceRNAs in Gastric Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1036
Author(s):  
Junhong Ye ◽  
Jifu Li ◽  
Ping Zhao
Keyword(s):  
Gastric Cancer ◽  
Research Strategy ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Cerna Network ◽  
Degree Of Malignancy ◽  
High Degree ◽  
Competitive Endogenous Rna ◽  
Made In

Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC’s mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC’s ceRNA network.

Long non‐coding RNAs (CASC2 and TUG1) in hepatocellular carcinoma: Clinical significance

2019 ◽  
Vol 21 (9) ◽  
Author(s):  
Noha S. Refai ◽  
Manal L. Louka ◽  
Hany Y. Halim ◽  
Iman Montasser
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Significance ◽  
Non Coding Rnas
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