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J Cell Physiol. 2020 Jan 22;:
Authors: Zhang Y, Zhang Z, Huang W, Zeng J
Abstract
Oral squamous cell carcinoma (OSCC) is the most aggressive type of head and neck cancer with an unsatisfactory 5-year survival rate. MicroRNAs are a group of small noncoding RNAs reported to serve important roles in carcinogenesis, inhibiting certain gene expression via targeting the 3'-untranslated region of messenger RNAs (mRNAs). MiR-4282 has been newly discovered to be a tumor suppressor in colorectal cancer, but it has never been studied in OSCC. The present study aimed to uncover the role of miR-4282 in OSCC. We first confirmed that miR-4282 was downregulated in OSCC and validated its prognostic significance. Through gain-of-function assays, miR-4282 was discovered to inhibit proliferation, migration, and epithelial-to-mesenchymal transition, and induce apoptosis. By mechanistic research, we predicted via bioinformatics tools and confirmed by luciferase reporter and pulldown assays that miR-4282 targeted LIN28B, an RNA-binding protein, which has been reported to regulate RNA stability in cancers. Furthermore, we confirmed the interaction between LIN28B and zinc finger and BTB domain containing 2 (ZBTB2), and validated that miR-4282 regulated mRNA stability of ZBTB2 by inhibiting LIN28B. Rescue assays proved that miR-4282 inhibited tumor progression through LIN28B/ZBTB2 axis. In vivo assays proved that miR-4282 inhibited tumor growth in OSCC. In conclusion, the present study revealed that miR-4282 inhibited tumor progression through downregulation of ZBTB2 by targeting LIN28B in OSCC cells, indicating miR-4282 as a novel biomarker for OSC.
PMID: 31970774 [PubMed - as supplied by publisher]
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