LncRNA H19 promotes the development of hepatitis B related hepatocellular carcinoma through regulating microRNA-22 via EMT pathway
Authors: Z-C Wang
G-J Shi
K Liu
L Li
T Han
C-G Lei
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA H19; hepatitis B-related hepatocellular carcinoma; prognosis; metastasis; overall survival
Affiliations: Department of Hepatobiliary Surgery, Qingdao Municipal Hospital of Shandong University, Qingdao, China. .

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. 

Retracted: No

PubPeer comments:
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 Fig 1D.  Kaplan-Meier survival curves of patients with HCC based on lncRNA H19 expression. Patients in high expression group had a significantly more unfavorable prognosis than those in low expression group . ![file] K-M plots of this form, resembling walls of Lego, are among the characteristic features of a papermill with products tabulated in a Google spreadsheet. https: docs.google.com spreadsheets d 1_762PbYYTCJhek5PdBuiDuN1q48UDgMa-rT6gi_jA8c edit?usp=sharing Fig 4D.  A negative correlation was found between lncRNA H19 expression and microRNA-22 expression in tumor samples . ![file] Rescaled for comparison with (right) a superimposition of 21 versions of the same scatterplot, from different papers. Darker data-points are included in more of the variants. ,