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

• Published in: Life sciences (1973) Vol. 284; p. 119708
• Main Authors: Shiu, Tzu-Yue, Lin, Hsuan-Hwai, Shih, Yu-Lueng, Feng, An-Chieh, Huang, Hsin-Hung, Huang, Tien-Yu, Hsieh, Chung-Bao, Chang, Wei-Kuo, Hsieh, Tsai-Yuan
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.11.2021; Elsevier BV
• Subjects: Binding sites; Cell proliferation; Correlation analysis; CRNDE-h; Cytokines; Hepatocellular carcinoma; Interleukin enhancer binding factor 2; Interleukins; Liver cancer; Malignancy; MicroRNAs; miR-136-5p; miRNA; Patients; Regulatory mechanisms (biology); Statistical analysis; Transcription; Western blotting; Interleukin enhancer binding factor 2; CRNDE-h; Hepatocellular carcinoma; miR-136-5p
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119708

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. 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. 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. 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. [Display omitted]