期刊
LIFE SCIENCES
卷 284, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119708
关键词
Hepatocellular carcinoma; Interleukin enhancer binding factor 2; miR-136-5p; CRNDE-h
资金
- Foundation for Medical Research of Tri-Service General Hospital and Ministry of Science and Technology [TSGH-C105-059, TSGH-C106-050, TSGH-C107-048, MOST 104-2314-B-016-006-, MOST 107-2314-B-016-037-]
This study identified miR-136-5p as a direct regulator of ILF2 in HCC and showed that the lncRNA CRNDE-h/miR-136-5p/ILF2 axis plays a significant role in the progression of HCC, potentially providing new targets for diagnosis, treatment, and prognosis of HCC.
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 miR136-5p 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.
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