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Journal of Environmental Pathology, Toxicology and Oncology
Factor de Impacto: 1.241 Factor de Impacto de 5 años: 1.349 SJR: 0.519 SNIP: 0.613 CiteScore™: 1.61

ISSN Imprimir: 0731-8898
ISSN En Línea: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2019028282
pages 119-131

Evaluation of LncRNA ANRIL Potential in Hepatic Cancer Progression

Yongjian Ji
Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, 324 JingwuWfeiqi Road, Jinan, Shandong Province 250021, China
Hao Sun
Department of Gastroenterology, Dezhou People's Hospital, 1751 Xinhu Road, Dezhou, Shandong Province 253014, China
Haiqing Liang
Department of Gastroenterology, Dezhou People's Hospital, 1751 Xinhu Road, Dezhou, Shandong Province 253014, China
Yong Wang
Department of Gastroenterology, Dezhou People's Hospital, 1751 Xinhu Road, Dezhou, Shandong Province 253014, China
Meili Lu
Department of Gastroenterology, Dezhou People's Hospital, 1751 Xinhu Road, Dezhou, Shandong Province 253014, China
Zhaoyang Guo
Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, 324 JingwuWfeiqi Road, Jinan, Shandong Province 250021, China
Zhuozhen Lv
Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, 324 JingwuWfeiqi Road, Jinan, Shandong Province 250021, China
Wanhua Ren
Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, 324 JingwuWfeiqi Road, Jinan, Shandong Province 250021, China

SINOPSIS

Background/Aims: LncRNAs are significant regulators in multiple cancers including hepatocellular carcinoma (HCC). Recently, lncRNA ANRIL has been reported to be elevated during multiple cancer types, exhibiting oncogenic roles. However, the exact biological mechanism of ANRIL is still poorly understood in HCC.
Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assays were utilized to detect expressions of ANRIL, miR-384, and STAT3. CCK8 and EDU assays were employed to evaluate HCC cell proliferation. A flow cytometry assay was used to detect the HCC cell cycle and cell apoptosis. The scratch migration and Transwell invasion assays were performed to test cell migration and invasion, respectively. RIP and RNA pull-down assays were carried out to confirm the correlation between ANRIL and miR-384. The dual-luciferase reporter assay was used to prove the association between miR-384 and STAT3. Western blotting analysis was performed to examine protein levels of STAT3. IHC and HE staining were employed to detect Ki-67 and histopathology.
Results: ANRIL expression was upregulated in HCC cells, including SMCC7721, HepG2, MHCC-97H, SNU449 and HUH-7 cells, in comparison to the normal human liver cells LO2. Knockdown of ANRIL suppressed HCC cell proliferation and induced cell cycle arrest and apoptosis. HCC cell migration and invasion capacity were inhibited by inhibition of ANRIL. Bioinformatics analyses revealed that ANRIL could interact with miR-384. miR-384 was significantly decreased in HCC cells, and overexpression of miR-384 repressed HCC progression. STAT3 was predicted as a target of miR-384, and miR-384 can modulate STAT3 levels negatively in vitro. ANRIL can suppress HCC development through regulating miR-384 and STAT3 in vivo.
Conclusion: ANRIL is involved in HCC progression by direct targeting of miR-384 and STAT3. Also, ANRIL could act as a potential candidate for HCC diagnosis, prognosis, and therapy.

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