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MiR‐4282 inhibits tumor progression through down‐regulation of ZBTB2 by targeting LIN28B in oral squamous cell carcinoma
Author(s) -
Zhang Ying,
Zhang Zebiao,
Huang Wanling,
Zeng Jinbiao
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29458
Subject(s) - biology , microrna , cancer research , carcinogenesis , cancer , untranslated region , rna binding protein , messenger rna , gene , genetics
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.