down-regulation of mir-135b in colon adenocarcinoma induced by a tgf-β receptor i kinase inhibitor (sd-208)

Authors

abolfazl akbari colorectal research center, rasoul-akram hospital, iran university of medical sciences, tehran, iran

mohammad hossein ghahremani department of pharmacology and toxicology, faculty of pharmacy, tehran university of medical sciences, tehran, iran

gholam reza mobini cellular and molecular research center, shahrekord university of medical sciences, shahrekord, iran

mahdi abastabar invasive fungi research center, department of medical mycology and parasitology, school of medicine, mazandaran university of medical sciences, sari, iran

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 sciences

جلد ۱۸، شماره ۹، صفحات ۸۵۶-۸۶۱

Keywords
[ ' c o l o n c a n c e r ' , ' o n c o g e n i c a n d s u p p r e s s o r m i c r o r n a s ( m i r n a s ) ' , ' s d ' , 2 0 8 , ' t g f ' , ' β r e c e p t o r 1 ( t g β r i ) k i n a s e i n h i b i t o r ' ]

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