CRNDE-h transcript/miR-136-5p axis regulates interleukin enhancer binding factor 2 expression to promote hepatocellular carcinoma cell proliferation.

Abstract

AIMS:

Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte. Interleukin enhancer binding factor 2 (ILF2) plays a role in the development of HCC. However, the regulatory mechanisms of ILF2 expression in HCC remain unclear. In this study, we aimed to identify ILF2-targeting microRNAs (miRNAs) and to explore how they affect ILF2 expression in HCC.

MAIN METHODS:

The tissue specimens were collected from 25 HCC patients. The underlying regulatory mechanism of ILF2 expression in HCC progression was determined using luciferase reporter assay, quantitative real-time PCR, Western blotting, and BrdU incorporation assay.

KEY FINDINGS:

Of predicted miRNA candidates (miR-122-5p, miR-425-5p, miR-136-5p, miR-7-5p, miR-421 and miR-543), a statistically significant inverse correlation by linear correlation analysis was observed between miR-136-5p and ILF2 mRNA expressions in patients with HCC (r = -0.627, P < 0.001). Further analysis demonstrated that ILF2 was directly regulated by miR-136-5p. In addition, we showed that long noncoding RNA colorectal neoplasia differentially expressed-h (lncRNA CRNDE-h) transcript expression was significantly up-regulated in HCC, and a miR-136-5p binding site was newly found in the lncRNA CRNDE-h transcript sequence using IntaRNA tool. In terms of mechanism, highly-expressed lncRNA CRNDE-h transcript can sponge miR-136-5p, thereby preventing it from interacting with target ILF2 mRNA while promoting the proliferation of HCC cells.

SIGNIFICANCE:

The lncRNA CRNDE-h/miR-136-5p/ILF2 axis plays a significant regulatory role in HCC progression, which may partly explain the pathogenic mechanisms of HCC and may provide promising potential targets for the diagnosis, treatment, and prognosis of HCC.

• Authors: Tzu-Yue Shiu, Hsuan-Hwai Lin, Yu-Lueng Shih, An-Chieh Feng, Hsin-Hung Huang, Tien-Yu Huang, Chung-Bao Hsieh, Wei-Kuo Chang, Tsai-Yuan Hsieh
• Journal: Life sciences (Life Sci) Vol. 284 Pg. 119708 (Nov 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 34153299 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• CRNDE RNA, human
• ILF2 protein, human
• MIRN136 microRNA, human
• MicroRNAs
• Nuclear Factor 45 Protein
• RNA, Long Noncoding
• RNA, Messenger

Topics

• Base Sequence
• Carcinoma, Hepatocellular (genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (genetics, pathology)
• MicroRNAs (genetics, metabolism)
• Nuclear Factor 45 Protein (genetics, metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)