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MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth
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نویسنده
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pu m. ,li c. ,qi x. ,chen j. ,wang y. ,gao l. ,miao l. ,ren j.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 7
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چکیده
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Micrornas (mirnas) are a class of small non-coding rnas,which direct post-transcriptional gene silencing (ptgs) and function in a vast range of biological events including cancer development. most mirnas pair to the target sites through seed region near the 5’ end,leading to mrna cleavage and/or translation repression. here,we demonstrated a mirna-induced dual regulation of heme oxygenase-1 (ho-1) via seed region and non-seed region,consequently inhibited tumor growth of nsclc. we identified mir-1254 as a negative regulator inhibiting ho-1 translation by directly targeting ho-1 3’utr via its seed region,and suppressing ho-1 transcription via non-seed region-dependent inhibition of transcriptional factor ap-2 alpha (tfap2a),a transcriptional activator of ho-1. mir-1254 induced cell apoptosis and cell cycle arrest in human non-small cell lung carcinoma (nsclc) cells by inhibiting the expression of ho-1,consequently suppressed nsclc cell growth. consistently with the in vitro studies,mouse xenograft studies validated that mir-1254 suppressed nsclc tumor growth in vivo. moreover,we found that ho-1 expression was inversely correlated with mir-1254 level in human nsclc tumor samples and cell lines. overall,these findings identify the dual inhibition of ho-1 by mir-1254 as a novel functional mechanism of mirna,which results in a more effective inhibition of oncogenic mrna,and leads to a tumor suppressive effect. © 2017 pu et al.
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آدرس
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center for drug safety evaluation and research,state key laboratory of drug research,shanghai institute of materia medica,chinese academy of sciences,shanghai,china,school of life science and technology,shanghaitech university,shanghai,china,university of chinese academy of sciences,beijing, China, center for drug safety evaluation and research,state key laboratory of drug research,shanghai institute of materia medica,chinese academy of sciences,shanghai,china,university of chinese academy of sciences,beijing, China, center for drug safety evaluation and research,state key laboratory of drug research,shanghai institute of materia medica,chinese academy of sciences,shanghai,china,university of chinese academy of sciences,beijing, China, center for drug safety evaluation and research,state key laboratory of drug research,shanghai institute of materia medica,chinese academy of sciences,shanghai,china,university of chinese academy of sciences,beijing, China, the brain science center,beijing institute of basic medical sciences,beijing, China, center for drug safety evaluation and research,state key laboratory of drug research,shanghai institute of materia medica,chinese academy of sciences,shanghai,china,university of chinese academy of sciences,beijing, China, center for drug safety evaluation and research,state key laboratory of drug research,shanghai institute of materia medica,chinese academy of sciences,shanghai,china,university of chinese academy of sciences,beijing, China, center for drug safety evaluation and research,state key laboratory of drug research,shanghai institute of materia medica,chinese academy of sciences,shanghai,china,university of chinese academy of sciences,beijing, China
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Authors
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