Abstract
Family with sequence similarity 83 (FAM83) members play important roles in carcinogenesis and tumor progression in several tumor types. However, the mechanism by which cancer cells regulate FAM83F still remains unclear. In this study, we found that the FAM84F protein and messenger RNA (mRNA) levels were consistently upregulated in esophageal squamous cell carcinoma (ESCC) tissues, which suggests that a post-transcriptional mechanism may be involved in the regulation of FAM83F. Since microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we performed bioinformatic analyses to search for miRNAs that could potentially target FAM83F. We identified the specific targeting site of miR-143 in the 3′-untranslated region (3′-UTR) of FAM83F and confirmed the inverse correlation between the levels of miR-143 and FAM83F protein and mRNA in ESCC tissue samples. By overexpressing or silencing miR-143 in ESCC cells, we experimentally validated that miR-143 directly binds to the 3′-UTR of the FAM83F transcript and degrades the FAM83F mRNA to regulate FAM83F expression. Furthermore, the biological consequences that miR-143 mediated by targeting FAM83F were examined using in vitro cell proliferation, apoptosis, migration, and invasion assays. We demonstrate that miR-143 exerted a tumor-suppressing effect by inhibiting the proliferation, migration, and invasion and inducing G1/G0 phase arrest of ESCC cells via the negative regulation of FAM83F expression. Taken together, our findings provide important evidence which supports the role of miR-143 as a tumor suppressor in ESCC via the inhibition of FAM83F expression.
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We declare that all human and animal studies have been approved by the hospital ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.
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An erratum to this article is available at http://dx.doi.org/10.1007/s13277-016-5470-7.
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Mao, Y., Liu, J., Zhang, D. et al. miR-143 inhibits tumor progression by targeting FAM83F in esophageal squamous cell carcinoma. Tumor Biol. 37, 9009–9022 (2016). https://doi.org/10.1007/s13277-015-4760-9
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DOI: https://doi.org/10.1007/s13277-015-4760-9