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MicroRNA-145 inhibits tumour growth and metastasis in colorectal cancer by targeting fascin-1.

Feng Y, Zhu J, Ou C, Deng Z, Chen M, Huang W, Li L - Br. J. Cancer (2014)

Bottom Line: In this study, miR-145 profiles were compared between CRC and corresponding non-tumour tissues.MiR-145 has a critical role in the inhibition of invasive and metastatic capacities of CRC, probably through directly targeting Fascin-1.This miRNA may be involved in the development and progression of CRC.

View Article: PubMed Central - PubMed

Affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, PR China [2] Department of Surgery, the Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, PR China.

ABSTRACT

Background: Recent studies have reported miR-145 dysregulated in colorectal cancer (CRC). In this study, miR-145 profiles were compared between CRC and corresponding non-tumour tissues.

Methods: The expression levels of miR-145 were analysed in CRC cell lines and tumour tissues by real-time PCR. A luciferase reporter assay confirmed direct targets. The functional effects of miR-145 were examined in transfected CRC cells in vitro and in vivo using established assays.

Results: Downregulation of miR-145 was detected in most primary CRC tumours, and was significantly correlated with a more aggressive phenotype of CRC in patients. In CRC cell lines, ectopic overexpression of miR-145 inhibited cell proliferation, motility and invasion in vitro. Stable overexpression of miR-145 suppressed tumour growth and pulmonary metastasis in vivo. Further studies indicated that miR-145 may directly interact with the 3'-untranslated region (3'-UTR) of Fascin-1 messenger RNA (mRNA), downregulating its mRNA and protein expression levels. In clinical specimens, Fascin-1 expression was negatively correlated with miR-145 expression.

Conclusions: MiR-145 has a critical role in the inhibition of invasive and metastatic capacities of CRC, probably through directly targeting Fascin-1. This miRNA may be involved in the development and progression of CRC.

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Related in: MedlinePlus

The effect of inhibition of miR-145 levels on cell proliferation, migration, invasion, and cell cycle distribution of CRC cell lines. Inhibition of miR-145 expression by transfecting miR-145 inhibitors into SW480 and HT-29 cell lines (A) significantly stimulates cell migration, invasion, and cell proliferation (C), compared with scramble controls (*P<0.05); however, it does not affect cell cycle distribution (D). Error bars (s.d.) were calculated from triplicate samples.
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fig3: The effect of inhibition of miR-145 levels on cell proliferation, migration, invasion, and cell cycle distribution of CRC cell lines. Inhibition of miR-145 expression by transfecting miR-145 inhibitors into SW480 and HT-29 cell lines (A) significantly stimulates cell migration, invasion, and cell proliferation (C), compared with scramble controls (*P<0.05); however, it does not affect cell cycle distribution (D). Error bars (s.d.) were calculated from triplicate samples.

Mentions: It was then determined whether miR-145 prevented metastatic-relevant traits from being acquired by non-metastatic human CRC cells. MiR-145 was transiently inhibited in non-metastatic SW480 and HT-29 cells with antisense oligonucleotides (Figure 3A). The suppression of miR-145 enhanced cell migration, invasion (Figure 3B), and cell proliferation (Figure 3C), but not cell cycle distribution (Figure 3D).


MicroRNA-145 inhibits tumour growth and metastasis in colorectal cancer by targeting fascin-1.

Feng Y, Zhu J, Ou C, Deng Z, Chen M, Huang W, Li L - Br. J. Cancer (2014)

The effect of inhibition of miR-145 levels on cell proliferation, migration, invasion, and cell cycle distribution of CRC cell lines. Inhibition of miR-145 expression by transfecting miR-145 inhibitors into SW480 and HT-29 cell lines (A) significantly stimulates cell migration, invasion, and cell proliferation (C), compared with scramble controls (*P<0.05); however, it does not affect cell cycle distribution (D). Error bars (s.d.) were calculated from triplicate samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4007224&req=5

fig3: The effect of inhibition of miR-145 levels on cell proliferation, migration, invasion, and cell cycle distribution of CRC cell lines. Inhibition of miR-145 expression by transfecting miR-145 inhibitors into SW480 and HT-29 cell lines (A) significantly stimulates cell migration, invasion, and cell proliferation (C), compared with scramble controls (*P<0.05); however, it does not affect cell cycle distribution (D). Error bars (s.d.) were calculated from triplicate samples.
Mentions: It was then determined whether miR-145 prevented metastatic-relevant traits from being acquired by non-metastatic human CRC cells. MiR-145 was transiently inhibited in non-metastatic SW480 and HT-29 cells with antisense oligonucleotides (Figure 3A). The suppression of miR-145 enhanced cell migration, invasion (Figure 3B), and cell proliferation (Figure 3C), but not cell cycle distribution (Figure 3D).

Bottom Line: In this study, miR-145 profiles were compared between CRC and corresponding non-tumour tissues.MiR-145 has a critical role in the inhibition of invasive and metastatic capacities of CRC, probably through directly targeting Fascin-1.This miRNA may be involved in the development and progression of CRC.

View Article: PubMed Central - PubMed

Affiliation: 1] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, PR China [2] Department of Surgery, the Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, PR China.

ABSTRACT

Background: Recent studies have reported miR-145 dysregulated in colorectal cancer (CRC). In this study, miR-145 profiles were compared between CRC and corresponding non-tumour tissues.

Methods: The expression levels of miR-145 were analysed in CRC cell lines and tumour tissues by real-time PCR. A luciferase reporter assay confirmed direct targets. The functional effects of miR-145 were examined in transfected CRC cells in vitro and in vivo using established assays.

Results: Downregulation of miR-145 was detected in most primary CRC tumours, and was significantly correlated with a more aggressive phenotype of CRC in patients. In CRC cell lines, ectopic overexpression of miR-145 inhibited cell proliferation, motility and invasion in vitro. Stable overexpression of miR-145 suppressed tumour growth and pulmonary metastasis in vivo. Further studies indicated that miR-145 may directly interact with the 3'-untranslated region (3'-UTR) of Fascin-1 messenger RNA (mRNA), downregulating its mRNA and protein expression levels. In clinical specimens, Fascin-1 expression was negatively correlated with miR-145 expression.

Conclusions: MiR-145 has a critical role in the inhibition of invasive and metastatic capacities of CRC, probably through directly targeting Fascin-1. This miRNA may be involved in the development and progression of CRC.

Show MeSH
Related in: MedlinePlus