LncRNA H19 promotes the development of hepatitis B related hepatocellular carcinoma through regulating microRNA-22 via EMT pathway.

Abstract

OBJECTIVE:

To explore the relationship between long non-coding RNA (lncRNA) H19 expression and prognosis of hepatitis B-related hepatocellular carcinoma (HBV-related HCC), and its underlying mechanism.

PATIENTS AND METHODS:

Expression level of lncRNA H19 in 36 HBV-related HCC tissues and para-cancerous tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The relationship between lncRNA H19 expression and prognosis of HBV-related HCC was analyzed by Kaplan-Meier method. Serum DNA levels of HBV were detected by fluorescence quantitative polymerase chain reaction (FQ-PCR). For in vitro experiments, lncRNA H19 expression in HCC cell line, HBV-related HCC cell line and normal liver cell line was detected by qRT-PCR. After plasmids construction, the effects of lncRNA H19 on cell viability, migration, and invasion were detected by cell counting kit-8 (CCK-8), colony formation and transwell assay, respectively. Finally, protein levels of epithelial-mesenchymal transition (EMT) pathway-related genes were detected by Western blot.

RESULTS:

LncRNA H19 was highly expressed in HBV-related HCC tissues. The expression of lncRNA H19 was positively correlated with lymph node metastasis and distant metastasis, whereas negatively correlated with the overall survival of HBV-related HCC patients. Results of in vitro experiments showed that lncRNA H19 knockdown significantly downregulated cell proliferation and invasion. However, lncRNA H19 knockdown significantly upregulated apoptosis of HBV-related HCC cells. Western blot results demonstrated that lncRNA H19 remarkably decreased the protein expressions of EMT pathway-related genes, including N-cadherin, Vimentin, β-catenin and MMP-9. In addition, rescue experiments demonstrated that lncRNA H19 remarkably promoted malignant development of HBV-related HCC via regulating microRNA-22.

CONCLUSIONS:

LncRNA H19 promotes malignant development of HBV-related HCC through regulating microRNA-22 via EMT pathway.

• Authors: L Li, T Han, K Liu, C-G Lei, Z-C Wang, G-J Shi
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 23 Issue 12 Pg. 5392-5401 (Jun 2019) ISSN: 2284-0729 [Electronic] Italy
• PMID: 31298392 (Publication Type: Journal Article, Observational Study)

Chemical References

• Biomarkers, Tumor
• H19 long non-coding RNA
• MIRN22 microRNA, human
• MicroRNAs
• RNA, Long Noncoding

Topics

• Apoptosis (genetics)
• Biomarkers, Tumor (analysis, metabolism)
• Carcinogenesis (genetics)
• Carcinoma, Hepatocellular (genetics, mortality, pathology, virology)
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease Progression
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Hep G2 Cells
• Hepatitis B (pathology, virology)
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms (genetics, mortality, pathology, virology)
• Lymphatic Metastasis (genetics, pathology)
• Male
• MicroRNAs (genetics)
• Middle Aged
• Prognosis
• RNA, Long Noncoding (analysis, metabolism)
• Up-Regulation