down-regulation of mir-135b in colon adenocarcinoma induced by a tgf-β receptor i kinase inhibitor (sd-208)
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abstract
objective(s):transforming growth factor-β(tgf-β) is involved in colorectal cancer (crc). the sd-208 acts as an anti-cancer agent in different malignancies via tgf-β signaling. this work aims to show the effect of manipulation of tgf-β signaling on some mirnas implicated in crc. materials and methods: we investigated the effects of sd-208 on sw-48, a colon adenocarcinoma cell line. the cell line was treated with 0.5, 1 and 2 μm concentrations of sd-208. then, the xenograft model of colon cancer was established by subcutaneous inoculation of sw-48 cell line into the nude mice. the animals were treated with sd-208 for three weeks. a quantitative real-time pcr was carried out for expression level analysis of selected oncogenic (mir-21, 31, 20a and 135b) and suppressor-mirnas (let7-g, mir-133b, 145 and 200c). data were analyzed using the 2-∆∆ct method through student’s t-test via the graphpad prism software. results: our results revealed that sd-208 could significantly down-regulate the expression of one key onco-mirna, mir-135b, in either sw-48 colon cells (p=0.006) or tumors orthotopically implanted in nude mice (p=0.018). our in silico study also predicted that sd-208 could modulate the expression of potential downstream tumor suppressor targets of the mir135b. conclusion: our data provide novel evidence that anticancer effects of sd-208 (and likely other tgf-β inhibitors) may be owing to their ability to regulate mirnas expression.
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Journal title:
iranian journal of basic medical sciencesجلد ۱۸، شماره ۹، صفحات ۸۵۶-۸۶۱
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