Dataset Information

The Similar Effects of miR-512-3p and miR-519a-2-5p on the Promotion of Hepatocellular Carcinoma: Different Tunes Sung With Equal Skill.

ABSTRACT: Although the therapeutic methods of hepatocellular carcinoma (HCC) have made great advances, the current situation is that HCC is the common malignancy. Our previous bioinformatic study presented that two members of C19MC (mir-512-1 and mir-519a-2) acted as crucial roles in the HCC progression. In this study, we first demonstrated that the miR-512-3p and miR-519a-2-5p, which were spliced from the mir-512-1 and mir-519a-2, were the functional mature miRNAs. Meanwhile, both miR-512-3p and miR-519a-2-5p were significantly upregulated in human HCC samples and HCC cell lines. The miR-512-3p and miR-519a-2-5p promoted the proliferation, invasion, and metastasis in vitro and in vivo. Moreover, the two miRNAs co-targeted the downstream tumor suppressors MAP3K2 and MAP2K4 and subsequently achieved the HCC progression. In the clinical cohort, high expression of miR-512-3p and miR-519a-2-5p acted as two risk factors for HCC recurrence and distinguished patients with poor tumor-free survival after radical resection. The integration of the two miRNAs into the AJCC staging system significantly improved the accuracy for the prediction of HCC recurrence. Our study suggests that miR-512-3p and miR-519a-2-5p have similar effects on the promotion of HCC progression. They can be robust markers for the prediction of HCC recurrence and therapy targets.

SUBMITTER: Rui T

PROVIDER: S-EPMC7427533 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Similar Effects of miR-512-3p and miR-519a-2-5p on the Promotion of Hepatocellular Carcinoma: Different Tunes Sung With Equal Skill.

Rui Tao T Zhang Xueyou X Feng Shi S Huang Haitao H Zhan Shaowei S Xie Haiyang H Zhou Lin L Ling Qi Q Zheng Shusen S

Frontiers in oncology 20200807

Although the therapeutic methods of hepatocellular carcinoma (HCC) have made great advances, the current situation is that HCC is the common malignancy. Our previous bioinformatic study presented that two members of C19MC (mir-512-1 and mir-519a-2) acted as crucial roles in the HCC progression. In this study, we first demonstrated that the miR-512-3p and miR-519a-2-5p, which were spliced from the mir-512-1 and mir-519a-2, were the functional mature miRNAs. Meanwhile, both miR-512-3p and miR-519a ...[more]

PMID: 32850377

Similar Datasets

Project description:BackgroundLiver metastasis (LM) is a major obstacle to the prognosis of gastric cancer (GC) patients, but the molecular mechanism underlying gastric cancer liver metastasis (GC-LM) remains unknown. Exosomes have been identified as an important mediator of communication between tumor cells and the microenvironment. Therefore, we sought to investigate the effects of primary GC cells on the liver microenvironment and the role of exosomal microRNAs (exo-miRNA) in GC-LM.MethodsSequential differential centrifugation, transmission electron microscopy and NanoSight analysis were used to extract and characterize exosomes. MicroRNA sequencing in GC-derived exosomes and mRNA sequencing in PMA-treated THP-1 cells were used to identify differentially expressed miRNAs in exosomes and the functional targets of exosomal miR-519a-3p (exo-miR-519a-3p) in macrophages, respectively. Tracing and internalization of exosomes and transfer of exo-miR-519a-3p were observed by immunofluorescence. Tubule formation assays, aortic ring assays, and exosome-educated GC-LM model were used to investigate the roles of GC-derived exosomes and exo-miR-519a-3p in angiogenesis and GC-LM. Luciferase reporter assay, qRT-PCR, Western blot, ELISA, flow cytometry and immunofluorescence were used to investigate the regulatory mechanism of exo-miR-519a-3p at GC-LM.ResultsThe expression level of miR-519a-3p in serum exosomes was significantly higher in GC-LM patients than in patients without LM, and high expression of exo-miR-519a-3p indicates a worse prognosis. GC-derived exosomes are mainly accumulated in the liver and internalized by intrahepatic macrophages. Mechanistically, exo-miR-519a-3p activates the MAPK/ERK pathway by targeting DUSP2, thereby causing M2-like polarization of macrophages. M2-like polarized macrophages accelerate GC-LM by inducing angiogenesis and promoting intrahepatic premetastatic niche formation.ConclusionsOur results indicate that exo-miR-519a-3p plays a critical role in mediating crosstalk between primary GC cells and intrahepatic macrophages and is a potential therapeutic target for GC-LM.

Project description:Background:Sustained proliferation and active metastasis are hallmarks of cancer, and they pose major challenges to the development of treatments and a cure for hepatocellular carcinoma (HCC). Thus, the mechanisms of proliferation, migration, and invasion of cancer cells need to be investigated. Many studies indicate that dysregulation of microRNA plays important roles in the progression of HCC, but the role of placenta-specific microRNA (miR-512-3p) in HCC has not been systematically investigated. Purpose:In the current study, the expression, biological function, and mechanisms of miR-512-3p involvement in HCC were investigated. Methods:Real-time quantitative polymerase chain reaction assays were conducted to determine miR-512-3p levels in HCC tissues and cell lines. The StarBase V3.0 online platform was used to compare miR-512-3p levels in HCC tissues with TCGA data and to identify potential miR-512-3p target genes. Associations between miR-512-3p and clinicopathological characteristics were analyzed statistically. MTT, ethynyl deoxyuridine, and transwell assays were performed to assess cell viability, proliferation, migration, and invasion. The luciferase reporter gene assay was used to verify target genes. Recuse assays were performed to confirm whether large tumor suppressor kinase 2 (LATS2) participated in the regulatory effects of miR-512-3p on HCC cell proliferation and motility, and whether miR-512-3p mediated the tumor-promoting effects of hypoxia. Results:miR-512-3p was upregulated in HCC and it was associated with worse survival and unfavorable clinicopathological characteristics. Functional assays indicated that miR-512-3p contributed to HCC cell proliferation, migration, and invasion. Mechanistically, LATS2-a downstream target of miR-512-3p-mediated the tumor-promoting effects of miR-512-3p in HCC. Hypoxia could elevate miR-512-3p levels in HCC cells, and miR-512-3p partially mediated the tumor-promoting effects of hypoxia. Conclusion:Hypoxia-induced miR-512-3p contributes to HCC cell proliferation, migration, and invasion by targeting LATS2 and inhibiting the Hippo/yes-associated protein 1 pathways.

Dataset Information

The Similar Effects of miR-512-3p and miR-519a-2-5p on the Promotion of Hepatocellular Carcinoma: Different Tunes Sung With Equal Skill.

Publications

The Similar Effects of miR-512-3p and miR-519a-2-5p on the Promotion of Hepatocellular Carcinoma: Different Tunes Sung With Equal Skill.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets