The Mechanism and Clinical Significance of Circular RNAs in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. In view of the lack of early obvious clinical symptoms and related early diagnostic biomarkers with high specificity and sensitivity, most HCC patients are already at the advanced stages at the time of diagnosis, and most of them are accompanied by distant metastasis. Furthermore, the unsatisfactory effect of the follow-up palliative care contributes to the poor overall survival of HCC patients. Therefore, it is urgent to identify effective early diagnosis and prognostic biomarkers and to explore novel therapeutic approaches to improve the prognosis of HCC patients. Circular RNA (CircRNA), a class of plentiful, stable, and highly conserved ncRNA subgroup with the covalent closed loop, is dysregulated in HCC. Increasingly, emerging evidence have confirmed that dysregulated circRNAs can regulate gene expression at the transcriptional or post-transcriptional level, mediating various malignant biological behaviors of HCC cells, including proliferation, invasion, metastasis, immune escape, stemness, and drug resistance, etc.; meanwhile, they are regarded as potential biomarkers for early diagnosis and prognostic evaluation of HCC. This article reviews the research progress of circRNAs in HCC, expounding the potential molecular mechanisms of dysregulated circRNAs in the carcinogenesis and development of HCC, and discusses those application prospects in the diagnosis and prognosis of HCC.

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Screening key genes related to ovarian cancer and exploring their possible molecular mechanisms

10.21203/rs.2.16321/v1 ◽

2019 ◽

Author(s):

Junzui Li ◽

Yuehua Zhang ◽

Zhixiong Huang ◽

Bin Zhao ◽

Ke Huang ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Diagnosis ◽

Candidate Genes ◽

Molecular Mechanisms ◽

Clinical Symptoms ◽

Malignant Tumors ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Hub Genes ◽

Key Genes

Abstract Background As one of the common malignant tumors in women, ovarian cancer (OC) often exerts the atypically early clinical symptoms. Therefore, it is particularly important for seeking more effectively early diagnosis of OC (biomarkers). Besides, although a lot of sequencing and chip research have been done on the pathogenesis of OC, the pathogenesis, clinical and genetic features of OC is still not very clear.Methods In this study, 4 GEO data (GSE66957, GSE119054, GSE14407 and GSE54388) were selected for differential expression gene analysis (DEGs), and the important template of the 4 DEGS overlapping genes was taken as Hub genes. Then, the GO and pathway enrichment analysis were conducted to confirm the enrichment of these Hub genes, and these Hub genes were identified as key genes. In addition, the transcriptional levels of these Hub genes in OC and their impacts on the overall survival rate of OC were validated via the UCSC and TCGA datasets.. Besides, cBioPortal, TargetScan, UCSC, DiseaseMeth and TIMER software were performed to explore the potential biological functions of these key genes in OC.Results We screened out 10 Hub genes related to OC including VEGFA, ZWINT, CDKN2A, SLC2A1, TOP2A, MKI67, CCND1, KPNA2, FGF2 and SMC4, and further demonstrated that they were most significantly enriched in protein binding, cytoplasm, nucleus, extracellular exosome, membrane, cell division, cell adhesion and pathways in cancer. Meanwhile, CCND1, TOP2A, SMC4 and FGF2 were screened out as key candidate genes associated with OC. Further analysis proved these key candidate genes may regulate the occurrence and development of OC through mediating the gene mutation, miRNAs and genetic epigenetics such as methylation and acetylation.Conclusion These data would improve our understanding of the causes and underlying molecular events of OC, be of clinical significance for the early diagnosis and prevention of OC, and may provide the promising therapeutic targets in OC.

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Research Progress of circRNA in Epithelial Mesenchymal Transformation of Gastric Cancer

10.20944/preprints201908.0258.v1 ◽

2019 ◽

Author(s):

Zhuoya Li ◽

Xiaoyun Ding ◽

Haojun Song

Keyword(s):

Gastric Cancer ◽

Molecular Mechanisms ◽

Malignant Tumors ◽

Treatment Success ◽

Research Direction ◽

Modern Medicine ◽

Research Progress ◽

Circular Rnas ◽

High Recurrence Rate ◽

Mesenchymal Transformation

With the continuous progress in modern medicine, the early detection rate of gastric cancer has increased, and the mortality rate has decreased. However, gastric cancer remains the third leading cause of cancer-related death worldwide, with a high recurrence rate. Metastasis is the leading cause of death and recurrence of gastric cancer, which greatly hinders treatment success. Cancer development is a complex process involving multiple sequential steps. In the metastatic cascade, local invasion may be considered an initial, crucial step in the development of a malignant tumor, which leads to distant metastasis. Epithelial-mesenchymal transformation (EMT) is one of the most important developmental processes that occur during tumor invasion. EMT confers certain basic abilities to cancer cells, such as migration, invasion and anti-apoptotic ability, thus initiating and increasing metastasis. However, little is known about the molecular mechanisms that promote EMT and gastric cancer cell metastasis. A number of recent studies have found that circular RNAs（circRNAs）are associated with gastric cancer EMT, regulating the EMT process and promoting the occurrence and development of tumors. Because of their unique continuous circular structure, circRNAs have relatively high stability in plasma and cells, making them more suitable as diagnostic biomarkers in malignant tumors. Therefore, understanding the mechanism of circRNAs in EMT in gastric cancer is an important research direction to actively prevent tumor metastasis and improve the therapeutic effect on advanced malignant tumors.

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Exosomal microRNAs in hepatocellular carcinoma

Cancer Cell International ◽

10.1186/s12935-021-01941-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chenbin Liu ◽

Han Wu ◽

Yinqi Mao ◽

Wei Chen ◽

Shuying Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Microenvironment ◽

Early Diagnosis ◽

Target Genes ◽

Malignant Tumors ◽

High Specificity ◽

Early Screening ◽

Active Mechanism ◽

Specificity And Sensitivity ◽

And Function

AbstractHepatocellular carcinoma is one of the most common malignant tumors worldwide and the fourth leading cause of cancer-related deaths. The prognosis of hepatocellular carcinoma patients is extremely poor due to the occult onset and high metastasis of hepatocellular carcinoma. Therefore, biomarkers with high specificity and sensitivity are of great importance in early screening, diagnosis prognosis, and treatment of hepatocellular carcinoma patients. Exosomes are tiny vesicles secreted by various types of cells, which can serve as mediators of intercellular communication to regulate the tumor microenvironment, and play a key role in the occurrence, development, prognosis, monitor and treatment of hepatocellular carcinoma. As microRNA deliverer, exosomes are involved in multiple life activities by regulating target genes of recipient cells such as proliferation, invasion, metastasis and apoptosis of cancer cells. In this review, we summarized the composition, active mechanism and function of exosomal microRNAs in hepatocellular carcinoma, and elaborated on their potential application value of early diagnosis and treatment in hepatocellular carcinoma.

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GCSF As a Potential Molecular Target for Overall Survival of Hepatocellular Carcinoma

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210322124003 ◽

2021 ◽

Vol 24 ◽

Author(s):

Heng Cao ◽

Peng Guo ◽

Xiaohui Wu ◽

Jiankun Li ◽

Chenlong Ge ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Survival Analysis ◽

Molecular Mechanisms ◽

Malignant Tumors ◽

Basic Research ◽

Clinical Samples ◽

Tumor Diameter ◽

Overall Survival Analysis

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of digestive tract in the world. Therefore, it is important to carry out studies on the molecular mechanisms of early diagnosis and treatment of HCC to reduce mortality. Methods: Bioinformatic analysis was performed to explore the significant role of GCSF on the occurrence and development of neoplasm. Differently expressed genes (DEGs) were screened, and the significant hub genes related with GCSF were identified by the multiple algorithms of Cytoscape. Functional annotation for DEGs, pathological stage and overall survival analysis were implemented. In addition, the verification for the role of GCSF on HCC was made via the clinical samples. A total of 70 participates diagnosed as HCC were recruited from November 2014 to November 2019. The immunohistochemistry assay, qRT-PCR, receiver operating characteristic (ROC) curves, and overall survival analysis were carried out. Results: GCSF was related with the tumor size, and the expression of GCSF was up-regulated in hepatocellular carcinoma tissues. The enrichment results of GO and KEGG analysis were mainly enriched in “Inflammatory response”, “Protein binding”, “Metabolic pathways”, and “Proteasome”. The tumor diameter (P < 0.001), and survival time (P < 0.001) were significantly associated with expression of GCSF via the verification of clinical data. The univariate and multivariate Cox proportional regression analysis manifested that high expression of GCSF in patients with HCC was related to poor OS. Conclusion: The expression level of GCSF is significantly associated with the prognostic survival of HCC, and it is expected to become a new prognostic marker of HCC, providing a novel idea for future basic research as well as targeted therapy.

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Identifying Potential Clinical Syndromes of Hepatocellular Carcinoma Using PSO-Based Hierarchical Feature Selection Algorithm

BioMed Research International ◽

10.1155/2014/127572 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Zhiwei Ji ◽

Bing Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Feature Selection ◽

Clinical Symptoms ◽

Malignant Tumors ◽

Feature Space ◽

Middle Layer ◽

Active Role ◽

Feature Representation ◽

Causal Relationships ◽

Positive Score

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Clinical symptoms attributable to HCC are usually absent, thus often miss the best therapeutic opportunities. Traditional Chinese Medicine (TCM) plays an active role in diagnosis and treatment of HCC. In this paper, we proposed a particle swarm optimization-based hierarchical feature selection (PSOHFS) model to infer potential syndromes for diagnosis of HCC. Firstly, the hierarchical feature representation is developed by a three-layer tree. The clinical symptoms and positive score of patient are leaf nodes and root in the tree, respectively, while each syndrome feature on the middle layer is extracted from a group of symptoms. Secondly, an improved PSO-based algorithm is applied in a new reduced feature space to search an optimal syndrome subset. Based on the result of feature selection, the causal relationships of symptoms and syndromes are inferred via Bayesian networks. In our experiment, 147 symptoms were aggregated into 27 groups and 27 syndrome features were extracted. The proposed approach discovered 24 syndromes which obviously improved the diagnosis accuracy. Finally, the Bayesian approach was applied to represent the causal relationships both at symptom and syndrome levels. The results show that our computational model can facilitate the clinical diagnosis of HCC.

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Research Progress of circRNAs in Head and Neck Cancers

Frontiers in Oncology ◽

10.3389/fonc.2021.616202 ◽

2021 ◽

Vol 11 ◽

Author(s):

Panchun Li ◽

Kunjie Zhu ◽

Yongzhen Mo ◽

Xiangying Deng ◽

Xianjie Jiang ◽

...

Keyword(s):

Head And Neck ◽

Malignant Tumors ◽

Treatment Resistance ◽

Disease Diagnosis ◽

Incidence Rates ◽

Head And Neck Cancers ◽

Research Progress ◽

Circular Rnas ◽

Patients With Cancer ◽

High Conservation

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Because of their characteristics of a closed loop structure, disease- and tissue-specificity, and high conservation and stability, circRNAs have the potential to be biomarkers for disease diagnosis. Head and neck cancers are one of the most common malignant tumors with high incidence rates globally. Affected patients are often diagnosed at the advanced stage with poor prognosis, owing to the concealment of anatomic sites. The characteristics, functions, and specific mechanisms of circRNAs in head and neck cancers are increasingly being discovered, and they have important clinical significance for the early diagnosis, treatment, and prognosis evaluation of patients with cancer. In this study, the generation, characteristics, and functions of circRNAs, along with their regulatory mechanisms in head and neck cancers have been summarized. We report that circRNAs interact with molecules such as transcription and growth factors to influence specific pathways involved in tumorigenesis. We conclude that circRNAs have an important role to play in the proliferation, invasion, metastasis, energy and substance metabolism, and treatment resistance in cancers.

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Comprehensive transcriptional profiling of aging porcine liver

PeerJ ◽

10.7717/peerj.6949 ◽

2019 ◽

Vol 7 ◽

pp. e6949 ◽

Cited By ~ 1

Author(s):

Jianning Chen ◽

Qin Zou ◽

Daojun Lv ◽

Muhammad Ali Raza ◽

Xue Wang ◽

...

Keyword(s):

Human Liver ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Genomic Structure ◽

Circular Rnas ◽

Transcriptional Level ◽

Porcine Liver ◽

Age Related ◽

Micro Rnas ◽

Model Animal

Background Aging is a major risk factor for the development of many diseases, and the liver, as the most important metabolic organ, is significantly affected by aging. It has been shown that the liver weight tends to increase in rodents and decrease in humans with age. Pigs have a genomic structure, with physiological as well as biochemical features that are similar to those of humans, and have therefore been used as a valuable model for studying human diseases. The molecular mechanisms of the liver aging of large mammals on a comprehensive transcriptional level remain poorly understood. The pig is an ideal model animal to clearly and fully understand the molecular mechanism underlying human liver aging. Methods In this study, four healthy female Yana pigs (an indigenous Chinese breed) were investigated: two young sows (180-days-old) and two old sows (8-years-old). High throughput RNA sequencing was performed to evaluate the expression profiles of messenger RNA, long non-coding RNAs, micro RNAs, and circular RNAs during the porcine liver aging process. Gene Ontology (GO) analysis was performed to investigate the biological functions of age-related genes. Results A number of age-related genes were identified in the porcine liver. GO annotation showed that up-regulated genes were mainly related to immune response, while the down-regulated genes were mainly related to metabolism. Moreover, several lncRNAs and their target genes were also found to be differentially expressed during liver aging. In addition, the multi-group cooperative control relationships and constructed circRNA-miRNA co-expression networks were assessed during liver aging. Conclusions Numerous age-related genes were identified and circRNA-miRNA co-expression networks that are active during porcine liver aging were constructed. These findings contribute to the understanding of the transcriptional foundations of liver aging and also provide further references that clarify human liver aging at the molecular level.

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The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/4044606 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Yanan Jiang ◽

Xiuyun Shen ◽

Moyondafoluwa Blessing Fasae ◽

Fengnan Zhi ◽

Lu Chai ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Circadian Rhythm ◽

Circadian Rhythms ◽

Molecular Mechanisms ◽

Therapeutic Targets ◽

Pathogenic Mechanism ◽

Research Progress ◽

Biological Processes ◽

And Function ◽

Novel Therapeutic

Hepatocellular carcinoma (HCC) is among the most common and lethal form of cancer worldwide. However, its diagnosis and treatment are still dissatisfactory, due to limitations in the understanding of its pathogenic mechanism. Therefore, it is important to elucidate the molecular mechanisms and identify novel therapeutic targets for HCC. Circadian rhythm-related genes control a variety of biological processes. These genes play pivotal roles in the initiation and progression of HCC and are potential diagnostic markers and therapeutic targets. This review gives an update on the research progress of circadian rhythms, their effects on the initiation, progression, and prognosis of HCC, in a bid to provide new insights for the research and treatment of HCC.

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CircRNA circ-0110102 Function as Anti-oncogenic Gene in Hepatocellular Carcinoma through Modulating miR-580-5p/CCL2 Pathway

10.21203/rs.3.rs-49964/v1 ◽

2020 ◽

Author(s):

Xinxing Wang ◽

Wei Sheng ◽

Tao Xu ◽

Jiawen Xu ◽

Juntao Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Mechanisms ◽

Tumor Biology ◽

Luciferase Assay ◽

Migration And Invasion ◽

Circular Rnas ◽

Dependent Manner ◽

Activation Effect ◽

Cox 2 ◽

No Activation

Abstract Background Circular RNAs (circRNAs) have been shown to have critical regulatory roles in tumor biology, whereas their contributions in hepatocellular carcinoma (HCC) still remains enigmatic. The purpose of this study was to investigate the molecular mechanisms involved in hsa_circ_0110102 in the occurrence and development of HCC. Results hsa_circ_0110102 was significantly down-regulated in HCC cell lines and tissues, low hsa_circ_0110102 expression levels were associated with poor prognosis. Knockdown hsa_circ_0110102 significantly inhibited cell proliferation, migration and invasion. In addition, the interaction between hsa_circ_0110102 and miR-580-5p was predicted and verified by luciferase assay and RNA pull-down, indicating that hsa_circ_0110102 function as sponge of miR-580-5p. Moreover, miR-580-5p which could directly bind to the 3’-UTR of CCL2 and induce its expression, then active the COX-2/PGE2 pathway in macrophage via FoxO1 in p38 MAPK dependent manner. Furthermore, the Δ256 mutant of FoxO1 showed no activation effect. These results concluded that hsa_circ_0110102 act as a sponge for miR-580-5p and decreased CCL2 secretion in HCC cells, then inhibits pro-inflammatory cytokine release from activated macrophage by regulating the COX-2/PGE2 pathway. Conclusions These results indicating that hsa_circ_0110102 serves as a potential prognostic predictor or therapeutic target for HCC.

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

Frontiers in Oncology ◽

10.3389/fonc.2021.696705 ◽

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.

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