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Abstract
BackgroundMicroRNA-21 (miR-21) is up-regulated in many cancers, including colorectal cancer (CRC). Nevertheless, the function of miR-21 in CRC and the mechanism underlying that function is still unclear.MethodsAfter analyzing the expression of miR-21 and Sec23A in CRC cell lines, we transfected the highest miR-21 expressing cell line, SW-480, with a plasmid containing an miR-21 inhibitor and the lowest miR-21 expressing cell line, DLD-1, with a plasmid containing an miR-21 mimic and measured the effects on the expression of Sec23A and on cell proliferation, migration, and invasion. We also evaluated the effect of knocking down Sec23A on miR-21 expression and its effects on cell proliferation, migration, and invasion. Finally, we assessed the effect of miR-21 in a xenograft tumor model in mice. Tumor tissues from these mice were subjected to immunohistochemical staining to detect the expression of Sec23A.ResultsGenetic deletion of miR-21 suppressed the proliferation, migration, and invasion of SW-480 cells, while over-expression of miR-21 promoted proliferation, migration, and invasion of DLD-1 cells. Inhibition of miR-21 increased the expression of Sec23A protein in SW-480 cells while over-expression of miR-21 significantly suppressed the expression of Sec23A protein and Sec23A mRNA in DLD-1 cells. Knockdown of Sec23A increased the expression of miR-21 in SW480 and DLD-1 cells and their proliferation (DLD-1 only), migration, and invasion. Over-expression of miR-21 promoted tumor growth in BALB/c nude mice and suppressed tumor expression of Sec23A.ConclusionThese findings provide novel insight into the molecular functions of miR-21 in CRC, which may serve as a potential interesting target.
Highlights
MicroRNA-21 is up-regulated in many cancers, including colorectal cancer (CRC)
MiR-21 overexpression stimulates proliferation, migration, and invasion of CRC cells Inhibition of miR-21 expression in SW-480 cells resulted in decreased proliferation, migration, and invasion compared with controls
There was no significant difference in expression of Sec23A messenger RNA (mRNA) between the SW-480 cells transfected with miR-21 inhibitor and controls (Fig. 3b)
Summary
MicroRNA-21 (miR-21) is up-regulated in many cancers, including colorectal cancer (CRC). Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide [1]. While chemotherapy is usually effective in reducing tumor cell growth and counteracting metastatic progression [2], it often loses efficacy, in advanced CRC through development of chemoresistance [3, 4], leading to disease recurrence and often patient death. MicroRNAs (miRNAs) belong to a class of small endogenous RNAs that influence many biological processes through binding to the 3′- untranslated region of target messenger RNA (mRNA), mediating either mRNA degradation or translational repression [5]. Aberrant miRNA expression is associated with many diseases, including cancers [6,7,8].
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