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. 2012 Apr 25:11:23.
doi: 10.1186/1476-4598-11-23.

MicroRNA-143 targets MACC1 to inhibit cell invasion and migration in colorectal cancer

Yu Zhang  1 , Zhongqiu Wang, Min Chen, Liang Peng, Xinying Wang, Qunying Ma, Fengli Ma, Bo Jiang
Affiliations

MicroRNA-143 targets MACC1 to inhibit cell invasion and migration in colorectal cancer

Yu Zhang et al. Mol Cancer. .

Abstract

Background: MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. Metastasis-associated in colon cancer-1 (MACC1) has been newly identified to express highly in colorectal cancer (CRC) and promote tumor metastasis through transactivating metastasis-inducing HGF/MET signaling pathway. In this study, we investigated whether miRNA 143 is involved in the regulation of MACC1 and thus plays a functional role in CRC. VSports手机版.

Results: Using both in silico prediction and western blot assay, we found the previously reported tumor suppressive miR-143 targeted MACC1 in CRC. The direct interaction between them was confirmed by 3' UTR luciferase reporter gene V体育安卓版. In concordance with the inhibitory effects induced by siRNA mediated knockdown of MACC1, restoration of miR-143 by mimics in SW620 cells significantly attenuated cell growth, migration and invasion. It is notable that combined treatment of miR-143 mimics and MACC1 siRNA induced synergistic inhibitory effects compared to either miR-143 mimics or MACC1 siRNA treatment alone. Conversely, reduction of miR-143 by inhibitors in SW480 cells apparently stimulated these phenotypes. Furthermore, we observed that miR-143 level was inversely correlated with MACC1 mRNA expression in CRC tissues. .

Conclusions: Our findings newly described miR-143/MACC1 link and provided a potential mechanism for MACC1 dysregulation and contribution to CRC cell invasion. It may help to estimate the therapeutic utility of miR-143 in CRC V体育ios版. .

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Figures

Figure 1
Figure 1
Decreased expression of miR-143 in both primary CRC tissues and CRC cell lines. (A) Decreased miR-143 expression (log10 scale at Y axis) in CRC tissues compared to the adjacent normal colonic tissues from a panel of 30 CRC patients (Wilcoxon's paired test, P = 0.006). (B) Significant loss of miR-143 expression in six CRC cell lines in comparison with control normal colonic mucosa pooled from 3 healthy individuals. Figure is representative of 3 experiments with similar results.
Figure 2
Figure 2
miR-143 directly targets MACC1 by binding to its 3'UTR. (A) The predicted miR-143 binding site within MACC1 3'UTR and its mutated version by site mutagenesis are as shown. (B) Variable MACC1 expression in six CRC cell lines was obtained by Western blot. β-actin was used as the loading control. (C) Non-metastatic SW480 cells expressed significantly higher level of miR-143 compared with its metastatic counterpart SW620 cells (* P < 0.05). (D) The repression of luciferase activity by MACC1 3'UTR was dependent on miR-143. Mutated MACC1 3'UTR abrogated miR-143 mediated repression luciferase activity (** P < 0.01). (E) In comparison with scramble controls, elevated expression of miR-143 by mimics inhibited MACC1 expression at both mRNA and protein level, while reduction of miR-143 by inhibitors moderately restored MACC1 expression (* P < 0.05). Figure is representative of 3 experiments with similar results.
Figure 3
Figure 3
Effects of miR-143 on proliferation, migration and invasion of SW620 and SW480 cell lines. (A) Ectopic expression of miR-143 by transfecting miR-143 mimics significantly reduced proliferation of SW620 cells, in comparison with parental and scramble controls (* P < 0.05). (B) Ectopic expression of miR-143 notably inhibited cell migration and invasion of SW620 cells (100 × magnification, * P < 0.05). Inversely, inhibition of miR-143 expression by transfecting miR-143 inhibitors simultaneously (C) promoted proliferation (*P < 0.05) and (D) stimulated cell migration and invasion of SW480 cells, compared with parental and scramble controls (100 × magnification, * P < 0.05). Figure is representative of 3 experiments with similar results.
Figure 4
Figure 4
Functional effects of MACC1 downregulation on SW620 cells. Inverse correlation between miR-143 and MACC1 expression in CRC. (A) Effectively suppression of MACC1 protein expression by MACC1 siRNA and miR-143 mimics respectively and combinedly. Note the more efficient suppression of MACC1 induced by combined treatment. Suppression of MACC1 simultaneously resulted in (B) significant inhibition of cell growth and (C) cell migration and invasion (100 × magnification) of SW620 cells compared with negative controls. Note the synergistic inhibitory effect induced by combination of MACC1 siRNA and miR-143 mimics, compared with either of them alone (*P < 0.05). The correlation between miR-143 and MACC1 mRNA expression by scatter plot. (D) An inverse correlation was observed in six CRC cell lines (Spearman' s correlation, r = -0.943, P = 0.005), and (E) also observed in another independent panel of 9 paired CRC tissues and adjacent normal tissues (Spearman's correlation, r = -0.48, P = 0.044). Figure is representative of 3 experiments with similar results.
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"VSports注册入口" References

    1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300. - PubMed
    1. Filipowicz W. RNAi: The nuts and bolts of the RISC machine. Cell. 2005;122:17–20. - PubMed
    1. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–355. - PubMed
    1. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11:228–234. - PubMed
    1. Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–269. - PubMed

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