Abstract
Recent studies have implied that aberration of miR-24 is linked to various human cancers. However, its role in non-small cell lung cancer (NSCLC) remains obscure. Here, we found that miR-24 was significantly upregulated in NSCLC tissues and patients’ serum. High expression of miR-24 in patients’ serum was independently correlated with a shorter overall survival of NSCLC patients. Depletion of miR-24 inhibited cell proliferation and anchorage-independent survival ability in lung cancer cell lines and reduced tumor formation ability in nude mice. Nuclear apoptosis-inducing factor 1 (NAIF1) was identified to be a functional target of miR-24 in the human lung. Next, we observed that the NAIF1 mRNA expression level in NSCLC tissues was suppressed in comparison to that in adjacent normal tissues. Restoration of NAIF1 in lung cancer cell inhibited cell proliferation and anchorage-independent survival ability, which were found to be similar with those from transfecting a miR-24 inhibitor into lung cancer cells. In conclusion, our study demonstrated that miR-24 was upregulated in NSCLC, and suppressing the expression of miR-24 inhibited tumor characteristics. MiR-24 acted as an oncomir, at least partially through regulation of its functional target NAIF1 in NSCLC. MiR-24 may serve as a novel potential biomarker for NSCLC diagnosis and prognosis.
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This work was supported in part by the Harbin Science and Technology Bureau (grant 2012RFQGJ183, Xian Liu).
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G. Zhao and L. Liu contributed equally to this work.
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Supplementary Fig. 1
a. Analysis of luciferase activity. A549 cells which have high endogenous miR-24 expression were cotransfected with firefly luciferase reporter containing 3′UTRs of interested genes, and Renilla luciferase expression construct (as an internal control). Luciferase activity was assayed 24 h after transfection. Firefly luciferase values, normalized for Renilla luciferase, are presented. The data represent the mean ± SE of four independent experiments done in duplicates. b. Western blot analysis of KSR2, FGF11, NAIF1, and β-actin in A549 cell extracts transfected with U6-miR-24 TuD plasmid. (TIFF 126 kb)
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Zhao, G., Liu, L., Zhao, T. et al. Upregulation of miR-24 promotes cell proliferation by targeting NAIF1 in non-small cell lung cancer. Tumor Biol. 36, 3693–3701 (2015). https://doi.org/10.1007/s13277-014-3008-4
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DOI: https://doi.org/10.1007/s13277-014-3008-4