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MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1.

Song M, Yin Y, Zhang J, Zhang B, Bian Z, Quan C, Zhou L, Hu Y, Wang Q, Ni S, Fei B, Wang W, Du X, Hua D, Huang Z - Protein Cell (2014)

Bottom Line: We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis.Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression.Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients.

View Article: PubMed Central - PubMed

Affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.

ABSTRACT
MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.

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MiR-139-5p inhibits CRC invasion via directly targeting AMFR and NOTCH1 in CRC. (A and B) The knockdown of AMFR or NOTCH1 by siRNA significantly repressed CRC cell invasion, which phenocopied the function of miR-139-5p, whereas the overexpression of AMFR or NOTCH1 (ORF without 3′UTR) markedly promoted cell invasion and counteracted miR-139-5p-induced invasion inhibition in LoVo cells
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Fig5: MiR-139-5p inhibits CRC invasion via directly targeting AMFR and NOTCH1 in CRC. (A and B) The knockdown of AMFR or NOTCH1 by siRNA significantly repressed CRC cell invasion, which phenocopied the function of miR-139-5p, whereas the overexpression of AMFR or NOTCH1 (ORF without 3′UTR) markedly promoted cell invasion and counteracted miR-139-5p-induced invasion inhibition in LoVo cells

Mentions: To examine the functional effect of AMFR and NOTCH1 in miR-139-5p-induced metastasis inhibition in CRC cells, we inhibited AMFR and NOTCH1 expression with siRNA (Fig. S6) and revealed that AMFR- and NOTCH1-depleted LoVo cells showed decreased invasion, which phenocopied the invasion-inhibiting effect of miR-139-5p. In contrast, the ectopic overexpression of AMFR and NOTCH1 using plasmids of AMFR and NOTCH1 (ICN) ORF promoted cell invasion, which could not be repressed by the overexpression of miR-139-5p (Fig. 5A and 5B). Taken together, these results proved that miR-139-5p inhibits CRC invasion through AMFR and NOTCH1.Figure 5


MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1.

Song M, Yin Y, Zhang J, Zhang B, Bian Z, Quan C, Zhou L, Hu Y, Wang Q, Ni S, Fei B, Wang W, Du X, Hua D, Huang Z - Protein Cell (2014)

MiR-139-5p inhibits CRC invasion via directly targeting AMFR and NOTCH1 in CRC. (A and B) The knockdown of AMFR or NOTCH1 by siRNA significantly repressed CRC cell invasion, which phenocopied the function of miR-139-5p, whereas the overexpression of AMFR or NOTCH1 (ORF without 3′UTR) markedly promoted cell invasion and counteracted miR-139-5p-induced invasion inhibition in LoVo cells
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4225484&req=5

Fig5: MiR-139-5p inhibits CRC invasion via directly targeting AMFR and NOTCH1 in CRC. (A and B) The knockdown of AMFR or NOTCH1 by siRNA significantly repressed CRC cell invasion, which phenocopied the function of miR-139-5p, whereas the overexpression of AMFR or NOTCH1 (ORF without 3′UTR) markedly promoted cell invasion and counteracted miR-139-5p-induced invasion inhibition in LoVo cells
Mentions: To examine the functional effect of AMFR and NOTCH1 in miR-139-5p-induced metastasis inhibition in CRC cells, we inhibited AMFR and NOTCH1 expression with siRNA (Fig. S6) and revealed that AMFR- and NOTCH1-depleted LoVo cells showed decreased invasion, which phenocopied the invasion-inhibiting effect of miR-139-5p. In contrast, the ectopic overexpression of AMFR and NOTCH1 using plasmids of AMFR and NOTCH1 (ICN) ORF promoted cell invasion, which could not be repressed by the overexpression of miR-139-5p (Fig. 5A and 5B). Taken together, these results proved that miR-139-5p inhibits CRC invasion through AMFR and NOTCH1.Figure 5

Bottom Line: We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis.Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression.Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients.

View Article: PubMed Central - PubMed

Affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.

ABSTRACT
MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.

Show MeSH
Related in: MedlinePlus