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Open AccessArticle

The Pivotal Role of Long Noncoding RNA RAB5IF in the Proliferation of Hepatocellular Carcinoma Via LGR5 Mediated β-Catenin and c-Myc Signaling

1
College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
2
Department of East-West Medical Science Graduate School of Kyung Hee University, Yongin 17104, Korea
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Biomolecules 2019, 9(11), 718; https://doi.org/10.3390/biom9110718
Received: 7 October 2019 / Revised: 30 October 2019 / Accepted: 30 October 2019 / Published: 8 November 2019
(This article belongs to the Section Molecular Biology)
In the current study, the function of long noncoding RNA (LncRNA) RAB5IF was elucidated in hepatocellular carcinoma (HCCs) in association with LGR5 related signaling. Here TCGA analysis revealed that LncRNA RAB5IF was overexpressed in HCC, and its overexpression level was significantly (p < 0.05) correlated with poor prognosis in patients with HCC. Furthermore, LncRNA RAB5IF depletion suppressed cell proliferation and colony formation, increased sub G1 population, cleavage of poly ADP-ribose polymerase (PARP) and cysteine aspartyl-specific protease (caspase 3) and attenuated the expression of procaspase 3, pro-PARP and B-cell lymphoma 2 (Bcl-2) in HepG2 and Hep3B cells. Furthermore, LncRNA RAB5IF depletion reduced the expression of LGR5 and its downstreams such as β-catenin and c-Myc in HepG2 and Hep3B cells. Notably, LGR5 depletion also attenuated the expression of pro-PARP, pro-caspase3, β-catenin and c-Myc in HepG2 and Hep3B cells. Conversely, LGR5 overexpression upregulated β-catenin and c-Myc in Alpha Mouse Liver 12 (AML-12) normal hepatocytes. Overall, these findings provide novel evidence that LncRNA RAB5IF promotes the growth of hepatocellular carcinoma cells via LGR5 mediated β-catenin and c-Myc signaling as a potent oncogenic target.
Keywords: long non-coding RNA; RAB5IF; LGR5; hepatocellular carcinoma; apoptosis long non-coding RNA; RAB5IF; LGR5; hepatocellular carcinoma; apoptosis
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MDPI and ACS Style

Koo, J.I.; Lee, H.-J.; Jung, J.H.; Im, E.; Kim, J.-H.; Shin, N.; Sim, D.Y.; Hwang, J.; Kim, S.-H. The Pivotal Role of Long Noncoding RNA RAB5IF in the Proliferation of Hepatocellular Carcinoma Via LGR5 Mediated β-Catenin and c-Myc Signaling. Biomolecules 2019, 9, 718.

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