Loss of TARBP2 Drives the Progression of Hepatocellular Carcinoma via miR-145-SERPINE1 Axis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA600937 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The clinical outcomes of hepatocellular carcinoma (HCC) remain dismal. Elucidating the molecular mechanisms for the progression of aggressive HCC holds the promise for developing novel intervention strategies. The transactivation response element RNA-binding protein (TRBP/TARBP2), a key component of microRNA (miRNA) processing and maturation machinery has exhibited to play conflicting roles in tumor development and progression. We sought to investigate the expression of TARBP2 in HCC using well-characterized HCC cell lines, patient-derived tissues and blood samples. Additionally, the potential prognostic and diagnostic value of TARBP2 in HCC were analyzed using Kaplan-Meier plots and ROC curve. Cell counting kit‐8 (CCK‐8), wound healing and transwell assays examined the ability of TARBP2 to induce cell proliferation, migration, and invasion in HCC cell lines. RNA sequencing was applied to identify the downstream elements of TARBP2. The interaction of potential targets of TARBP2, miR‐145 and serpin family E member 1 (SERPINE1), was assessed using luciferase reporter assay. TARBP2 expression was down-regulated in HCC cell lines relative to normal hepatocyte cells, with a similar pattern further confirmed in tissue and blood samples. Notably, the loss of TARBP2 was demonstrated to promote proliferation, migration, and invasion in HCC cell lines. Interestingly, the reduction of TARBP2 was shown to result in the upregulation of SERPINE1, also known as plasminogen activator inhibitor (PAI-1), which is a vital gene of the HIF-1 signaling pathway. Knockdown of SERPINE1 rescued the TARBP2-lost phenotype. Moreover, TARBP2 depletion induced the upregulation of SERPINE1 through reducing the processing of miR-145, which directly targets SERPINE1. Finally, overexpression of miR-145 repressed SERPINE1 and rescued the functions in sh-TARBP2 HCC cells. Our findings underscore a linear TARBP2-miR-145-SERPINE1 pathway that drives HCC progression, with the potential as a novel intervention target for aggressive HCC.
2021-05-26 | GSE143551 | GEO
Project description: Not available
| S-EPMC8265608 | biostudies-literature
Project description:We have recently demonstrated that human paediatric mesenchymal stem cells can be reprogrammed toward a Ewing’s sarcoma family tumor (ESFT) cancer stem cell (CSC) phenotype by mechanisms that implicate microRNAs (miRNAs). Here, we show that the miRNA profile of ESFT CSC is shared by embryonic stem cells and CSC from divergent tumor types. We also provide evidence that the miRNA profile of ESFT CSC is the result of reversible disruption of TARBP2-dependent miRNA maturation. Restoration of TARBP2 activity and systemic delivery of synthetic forms of either of two of its targets, miRNA-143 or miRNA-145, inhibited ESFT CSC clonogenicity and tumor growth in vivo. Our observations suggest that CSC self-renewal and tumor initiation may depend on deregulation of TARBP2-dependent miRNA expression.
2012-06-20 | GSE31144 | GEO
Project description:We have recently demonstrated that human paediatric mesenchymal stem cells can be reprogrammed toward a Ewing’s sarcoma family tumor (ESFT) cancer stem cell (CSC) phenotype by mechanisms that implicate microRNAs (miRNAs). Here, we show that the miRNA profile of ESFT CSC is shared by embryonic stem cells and CSC from divergent tumor types. We also provide evidence that the miRNA profile of ESFT CSC is the result of reversible disruption of TARBP2-dependent miRNA maturation. Restoration of TARBP2 activity and systemic delivery of synthetic forms of either of two of its targets, miRNA-143 or miRNA-145, inhibited ESFT CSC clonogenicity and tumor growth in vivo. Our observations suggest that CSC self-renewal and tumor initiation may depend on deregulation of TARBP2-dependent miRNA expression. 3 Ewing sarcoma cell lines: comparison between TARBP2 silencing by shRNA and control.
2012-06-19 | E-GEOD-31144 | biostudies-arrayexpress
Project description:In order to identify TARBP2 binding sites on endogenous RNA, we performed HITS-CLIP on a myc-tagged TARBP2 expressing cell-line (transient transfection)
2014-07-24 | GSE49648 | GEO
Project description:In order to identify TARBP2 binding sites on endogenous RNA, we performed HITS-CLIP on a myc-tagged TARBP2 expressing cell-line (transient transfection) Cells were transfected with tagged TARBP2 vector (Origene) and 48-hr post-transfection, they were subjected to the HITS-CLIP procedure (Licatalosi D, et al. 2008, Nature 456:464-U22)
2014-07-24 | E-GEOD-49648 | biostudies-arrayexpress
Project description:To identify changes in splicing patterns following TARBP2 knockdiwn, RNA-sequencing was performed on breast cancer cells transfected with siRNAs targeting TARBP2.
2019-12-26 | GSE130872 | GEO
Project description:To identify changes in splicing patterns following TARBP2 knockdown, RNA-sequencing was performed on breast cancer cells transduced with shRNAs targeting TARBP2.
2019-12-26 | GSE130869 | GEO
Project description:To identify changes in splicing patterns following TARBP2 knockdown, RNA-sequencing was performed on nuclear RNA extracted from cells expressing shRNAs targeting TARBP2 or a non-targeting shRNA (shControl).
2019-12-26 | GSE130870 | GEO
Project description:To identify changes in methylation patterns following TARBP2 knockdown, m6A-IP followed by RNA-seq was performed on breast cancer cells expressing shRNAs against TARBP2 (and non-targeting shControl cells).
2019-12-26 | GSE130893 | GEO