scholarly journals The Role of Long Non-Coding RNA and microRNA Networks in Hepatocellular Carcinoma and Its Tumor Microenvironment

2021 ◽  
Vol 22 (19) ◽  
pp. 10630
Author(s):  
Tingting Shi ◽  
Asahiro Morishita ◽  
Hideki Kobara ◽  
Tsutomu Masaki
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
High Morbidity ◽  
Liver Malignancy ◽  
Non Coding Rna ◽  
Tumorigenesis And Progression ◽  
Microrna Networks ◽  
Regulatory Effects ◽  
Long Non Coding Rna

Hepatocellular carcinoma (HCC) is a common liver malignancy with high morbidity and poor prognosis. Long non-coding RNAs (lncRNAs) are involved in crucial biological processes of tumorigenesis and progression, and play four major regulatory roles, namely signal, decoy, guide, and scaffold, to regulate gene expression. Through these processes, lncRNAs can target microRNAs (miRNAs) to form lncRNA and miRNA networks, which regulate cancer cell proliferation, metastasis, drug resistance, and the tumor microenvironment. Here, we summarize the multifaceted functions of lncRNA and miRNA networks in the pathogenesis of HCC, the potential use of diagnostic or prognostic biomarkers, and novel therapeutic targets in HCC. This review also highlights the regulatory effects of lncRNA and miRNA networks in the tumor microenvironment of HCC.

Long non-coding RNA ZEB1-AS1 promotes proliferation and metastasis of hepatocellular carcinoma cells by targeting miR-299-3p/E2F1 axis

2021 ◽  
Author(s):  
Baiyin Mu ◽  
Chenlan Lv ◽  
Qingli Liu ◽  
Hong Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Non Coding Rna ◽  
Tumorigenesis And Progression ◽  
Novel Biomarkers ◽  
Proliferation And Metastasis ◽  
Long Non Coding Rna

Abstract There is emerging evidence that dysregulation of long non-coding RNAs (lncRNAs) is associated with hepatocellular carcinoma (HCC). Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) functions as an oncogenic regulator in various malignancies. Nonetheless, the potential role of ZEB1-AS1 in HCC remains poorly elucidated. Herein, qRT-PCR was employed for examining ZEB1-AS1, miR-299-3p and E2F1 mRNA expressions in HCC cells and tissues. MTT assay was performed to evaluate cell proliferation. Transwell assay was utilized for evaluating cancer cell migration and invasion. Western blot was employed for measuring E2F1 protein expression. What’s more, dual-luciferase reporter assay was utilized for verifying the targeting relationships between ZEB1-AS1 and miR-299-3p, as well as E2F1 and miR-299-3p. It was demonstrated that, in HCC tissues and cells, ZEB1-AS1 expression was markedly increased, and meanwhile, its high expression level is related to the unfavorable clinicopathologic indicators. ZEB1-AS1 overexpression facilitated HCC cell proliferation, migration and invasion, while its knockdown led to the opposite effects. In terms of mechanism, we discovered that ZEB1-AS1 could decoy miR-299-3p and up-regulate E2F1 expression. This work reveals the functions and mechanism of ZEB1-AS1 in HCC tumorigenesis and progression, which provides novel biomarkers and therapeutic targets for HCC.

scholarly journals Prognostic value of an immune long non-coding RNA signature in liver hepatocellular carcinoma

2019 ◽  
Author(s):  
rui kong ◽  
Nan Wang ◽  
Wei Han ◽  
Yuejuan Zheng ◽  
Jie Lu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Risk Groups ◽  
Gene Set Enrichment Analysis ◽  
Kaplan Meier ◽  
Non Coding Rna ◽  
Liver Hepatocellular Carcinoma ◽  
Long Non Coding Rna

Abstract Background: In recent years, long non-coding RNAs (lncRNAs) are emerging as crucial regulators in the immunological process of liver hepatocellular carcinoma (LIHC). Increasing studies have found that some lncRNAs could be used as a diagnostic or therapeutic target for clinical management, but little research has investigated the role of immune-related lncRNA in tumor prognosis. In this study, we aimed to develop an immune lncRNA signature for the precise diagnosis and prognosis of liver hepatocellular carcinoma. Methods: Gene expression profiles of LIHC samples obtained from TCGA were screened for immune-related genes using two reference gene sets. The optimal immune-related lncRNA signature was built via correlational analysis, univariate and multivariate cox analysis. Then the Kaplan-Meier plot, ROC curve, clinical analysis, gene set enrichment analysis, and principal component analysis were carried out to evaluate the capability of immune lncRNA signature as a prognostic indicator. Results: Six long non-coding RNA MSC−AS1, AC009005.1, AL117336.3, AL031985.3, AL365203.2, AC099850.3 were identified via correlation analysis and cox regression analysis considering their interactions with immune genes. Next, tumor samples were separated into two risk groups by the signature with different clinical outcomes. Stratification analysis showed the prognostic ability of this signature acted as an independent factor. The AUC value of ROC curve was 0.779. The Kaplan-Meier method was used in survival analysis and results showed a statistical difference between the two risk groups. The predictive performance of this signature was validated by principal component analysis (PCA). Data from gene set enrichment analysis (GSEA) further unveiled several potential biological processes of these biomarkers may involve in. Conclusion: In summary, the study demonstrated the potential role of the six-lncRNA signature served as an independent prognostic factor for LIHC patients.

The role of the long non-coding RNA TDRG1 in epithelial ovarian carcinoma tumorigenesis and progression through miR-93/RhoC pathway

2017 ◽  
Vol 57 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Shuo Chen ◽  
Li-li Wang ◽  
Kai-Xuan Sun ◽  
Yin-ling Xiu ◽  
Zhi-Hong Zong ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Epithelial Ovarian Carcinoma ◽  
Non Coding Rna ◽  
Tumorigenesis And Progression ◽  
Long Non Coding Rna

scholarly journals PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Allen T Yu ◽  
Carmen Berasain ◽  
Sonam Bhatia ◽  
Keith Rivera ◽  
Bodu Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Level ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Rna Seq ◽  
Liver Malignancy ◽  
Translational Repressor ◽  
Non Coding Rna ◽  
And Migration ◽  
Long Non Coding Rna

Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is over-expressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a Myc motif in their promoter. MYC is decreased at the protein level, but not the mRNA level. RNA-antisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases MYC translation. In summary, our data suggest that PHAROH regulates MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma.

Long Non-Coding RNA CASC7 Promotes Proliferation and Inhibits Apoptosis of Hepatocellular Carcinoma Cells via Downregulating miR-340-5p CASC7/miR-340-5p Axis in Hepatocellular Carcinoma

2022 ◽  
Vol 12 (4) ◽  
pp. 747-755
Author(s):  
Shengyong Liu ◽  
Xiangcheng Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Nrf2 Pathway ◽  
Non Coding Rna ◽  
Tumorigenesis And Progression ◽  
Long Non Coding Rna ◽  
Dual Luciferase Reporter Assay

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide with a poor prognosis. Amounting studies revealed that long non-coding RNAs (lncRNAs) show important roles in various biological processes. The purpose of this study was to explore the biological function and potential molecular mechanism of CASC7 in HCC. Methods: CASC7 expression in HCC cell lines was detected by qRT-PCR. The expressions of CASC7 and miR-340-5p were changed by transfection of miR-340-5p mimic, the CASC7 overexpression and knockdown plasmids. The interaction between CASC7 and miR-340-5p was assessed by a Dual-Luciferase reporter assay. The biological functions of CASC7 were evaluated by CCK-8, colony formation assay, ROS assay kit, immunofluorescence and flow cytometry (FCM). Results: CASC7 was upregulated in HCC cell lines. CASC7 overexpression significantly promoted cell proliferation, as well as inhibited apoptosis and oxidative stress. In contrast, CASC7 knockdown could reverse these above changes. The result of the Dual-luciferase reporter assay revealed that CASC7 directly targeted miR-340-5p and negatively regulated its expression. In addition, CASC7 promoted proliferation and inhibited apoptosis of HCC cells through activating Nrf2 pathway by downregulating miR-340-5p. Conclusions: In summary, CASC7 promotes HCC tumorigenesis and progression through the Nrf2 pathway by targeting miR-340-5p, which may provide a new target for therapy of HCC.

scholarly journals Role of the long non-coding RNA HOTAIR in hepatocellular carcinoma

2017 ◽  
Vol 14 (2) ◽  
pp. 1233-1239 ◽  
Author(s):  
Liming Wu ◽  
Lele Zhang ◽  
Shusen Zheng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Development and Validation of a Pyroptosis-Related Long Non-coding RNA Signature for Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Zeng-Hong Wu ◽  
Zi-Wei Li ◽  
Dong-Liang Yang ◽  
Jia Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Tumor Microenvironment ◽  
Risk Score ◽  
Low Risk ◽  
Lasso Regression ◽  
Non Coding Rna ◽  
Novel Biomarkers ◽  
Development And Validation ◽  
Long Non Coding Rna

Background: Hepatocellular carcinoma (HCC) is a highly aggressive malignant disease, and numerous studies have demonstrated that an inflammatory environment can induce normal cells to transform into cancerous.Methods: We integrated genomic data to comprehensively assess the association between pyroptosis and tumor microenvironment (TME) cell-infiltrating characteristics in HCC, as well as the potential molecular function and clinical significance of lncRNA.Results: The analysis of CNV alteration frequency displayed that CNV changes were common in 33 PRGs, and most were focused on copy number amplification. As a result of lasso regression analysis, nine differentially expressed lncRNAs (AL031985.3, NRAV, OSMR-AS1, AC073611.1, MKLN1-AS, AL137186.2, AL049840.4, MIR4435-2HG, and AL118511.1) were selected as independent prognosis factors of HCC patients. Patients at high risk have poorer survival than those in the low-risk group in training and testing cohorts. A low-risk score was significantly associated with an IC50 of chemotherapeutics such as bortezomib (p < 0.001), but a high-risk score was significantly linked to docetaxel (p < 0.001), implying that signature served as a prospective predictor for chemosensitivity.Conclusion: This work suggests pyroptosis-related lncRNAs features and their potential mechanisms on tumor microenvironment. The exploration may assist in identifying novel biomarkers and assist patients in predicting their prognosis, clinical diagnosis, and management.

scholarly journals PHAROH lncRNA regulates c-Myc translation in hepatocellular carcinoma via sequestering TIAR

2021 ◽  
Author(s):  
Allen T Yu ◽  
Carmen Berasain ◽  
Sonam Bhatia ◽  
Keith Rivera ◽  
Bodu Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Level ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Rna Seq ◽  
Liver Malignancy ◽  
Translational Repressor ◽  
Non Coding Rna ◽  
And Migration ◽  
Long Non Coding Rna

Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is overexpressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a c-Myc motif in their promoter. C-MYC is decreased at the protein level, but not the mRNA level. RNAantisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases c-MYC translation. In summary, our data suggest that PHAROH regulates c-MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma.

The role of long non-coding RNA PCA3 in epithelial ovarian carcinoma tumorigenesis and progression

Gene ◽  
2017 ◽  
Vol 633 ◽  
pp. 42-47 ◽  
Author(s):  
Yao Liu ◽  
Zhi-Hong Zong ◽  
Xue Guan ◽  
Li-li Wang ◽  
Yang Zhao
Keyword(s):  
Ovarian Carcinoma ◽  
Epithelial Ovarian Carcinoma ◽  
Non Coding Rna ◽  
Tumorigenesis And Progression ◽  
Long Non Coding Rna

scholarly journals Role of long non-coding RNA H19 in therapy resistance of digestive system cancers

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jingting Wang ◽  
Xiao Ma ◽  
Hai Si ◽  
Zhongjun Ma ◽  
Yan Ma ◽  
...  
Keyword(s):  
Digestive System ◽  
Therapy Resistance ◽  
Treatment Modalities ◽  
Ductal Adenocarcinoma ◽  
High Morbidity ◽  
Expression Of Genes ◽  
Dismal Prognosis ◽  
Non Coding Rna ◽  
Long Non Coding Rna

AbstractDigestive system cancers are associated with high morbidity and mortality. Chemotherapy and radiotherapy are the main treatment modalities for these cancers. However, the development of therapy resistance leads to high rates of tumor recurrence and metastasis, resulting in dismal prognosis. Long non-coding RNA (LncRNA) H19, one of the most intriguing non-coding RNAs, has been shown to play a key role in the development and therapy resistance of various digestive system cancers (including hepatocellular carcinoma, colorectal cancer, pancreatic ductal adenocarcinoma, esophageal carcinoma, gastric cancer, and biliary system cancer) by regulating the abnormal expression of genes. In this review, we discuss the potential mechanisms of LncRNA H19 related therapy resistance in the context of digestive system cancers. LncRNA H19 is a potential novel therapeutic target for amelioration of cancer therapy resistance.

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