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MicroRNA-490-3p inhibits colorectal cancer metastasis by targeting TGFβR1.

Xu X, Chen R, Li Z, Huang N, Wu X, Li S, Li Y, Wu S - BMC Cancer (2015)

Bottom Line: Artificially overexpression miR-490-3p in CRC cell lines inhibited cell migration and invasion abilities while knockdown miR-490-3p expression caused the reverse effects.Inhibition of TGFβR1 could partially recover the tumor suppression effect of miR-490-3p. miR-490-3p is downregulated during CRC malignant progression. miR-490-3p represses CRC cell migration and invasion abilities, partially by targeting to the TGF-β signaling pathway.Taken together, miR-490-3p is acting as a tumor suppressor in CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastrointestinal Surgery, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. xxh@gzhmu.edu.cn.

ABSTRACT

Background: Colorectal cancer (CRC) is one of the most common malignances worldwide. Metastasis is responsible for the rapid recurrence and poor prognosis of CRC. However, the underlying molecular mechanism of CRC metastasis remains largely unclear. In this study we purposed to investigate the expression and biological functions of miR-490-3p in CRC metastasis, as well as to identify its downstream target genes and influenced pathway.

Methods: The expression level of miR-490-3p in CRC cell lines, CRC adjacent normal tissues, non-metastasis and metastasis tissues were assessed by quantitative real-time PCR. Patient survivals were follow-up up to 7 years. Gain-of-function and loss-of-function study on cell migration and invasion abilities were carried out by transfection of miR-490-3p mimics or inhibitors respectively. The molecular targets of miR-490-3p were computationally identified and experimentally verified by dual-luciferase reporter assay and western blot. Functional rescue was also conducted to confirm miR-490-3p inhibits CRC metastasis by targeting TGF-β signaling pathway.

Results: miR-490-3p expression was persistently downregulated during CRC malignant progression, as well as in CRC cell lines. Artificially overexpression miR-490-3p in CRC cell lines inhibited cell migration and invasion abilities while knockdown miR-490-3p expression caused the reverse effects. TGFβR1 and MMP2/9 were the downstream targets of miR-490-3p in CRC. Inhibition of TGFβR1 could partially recover the tumor suppression effect of miR-490-3p.

Conclusion: miR-490-3p is downregulated during CRC malignant progression. miR-490-3p represses CRC cell migration and invasion abilities, partially by targeting to the TGF-β signaling pathway. Taken together, miR-490-3p is acting as a tumor suppressor in CRC.

No MeSH data available.


Related in: MedlinePlus

Downregulation of miR-490-3p in human CRC tissues and cell lines. a Global miRNA expression profile revealed miR-490-3p was downregulated in CRC tissues versus non-neoplastic colon. Each row of the heatmap indicated one tissue sample and each column indicated one miRNA. Labels in the right represented for miRNA symbol or probeset. Red: high expression; Green: low expression. b Quantitative real-time PCR analysis of miR-490-3p expression in 8 pairs of CRC tumor and adjacent non-tumor tissue samples. c Quantitative real-time PCR analysis of miR-490-3p expression in 8 CRC cell lines. *: A two-tailed t-test P-value <0.05
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Fig1: Downregulation of miR-490-3p in human CRC tissues and cell lines. a Global miRNA expression profile revealed miR-490-3p was downregulated in CRC tissues versus non-neoplastic colon. Each row of the heatmap indicated one tissue sample and each column indicated one miRNA. Labels in the right represented for miRNA symbol or probeset. Red: high expression; Green: low expression. b Quantitative real-time PCR analysis of miR-490-3p expression in 8 pairs of CRC tumor and adjacent non-tumor tissue samples. c Quantitative real-time PCR analysis of miR-490-3p expression in 8 CRC cell lines. *: A two-tailed t-test P-value <0.05

Mentions: As described before, dual-faced functional roles of miR-490-3p have been found in various cancers, however, its correlation with CRC remains largely unknown, which prompt us to explore its expression and function in CRC. After data mining of previously reported global miRNA expression profiles of 54 cancerous and 20 non-cancerous colonic tissues [13], we identified a miRNA, miR-490-3p, was downregulated in majority of CRC samples (Fig. 1a). By quantitative real-time PCR determination, we confirmed the decreasing expression of miR-490-3p in 8 pairs of CRC tumor and adjacent non-tumor tissue samples (Fig. 1b), as well as in all the 8 CRC cell lines (HT29, SW620, SW480, HCT-15, LS174T, HCT116, LoVo, DLD-1) analyzed in this study (Fig. 1c, P < 0.05). Although wide expression discrepancies had been found among these patient samples and cell lines, individual heterogeneity and the complexity of clinical samples (including different tumor stage, tumor size, patient age and gender, and etc.) still do not mask this decreasing tendency. Moreover, miR-490-3p expression was further downregulated in fifteen metastasis CRC samples, in comparison with the expression level in fifteen matched non-metastasis CRC samples (Fig. 2a, P < 0.05). Following-up of these patients indicated lower expression level of miR-490-3p was associated with poor prognosis of survival (Fig. 2b, P < 0.05). Taken together, miR-490-3p expression was downregulated during CRC tumorigenesis and malignant progression. miR-490-3p perhaps acts as a tumor suppressor in CRC, which would be determined below.Fig. 1


MicroRNA-490-3p inhibits colorectal cancer metastasis by targeting TGFβR1.

Xu X, Chen R, Li Z, Huang N, Wu X, Li S, Li Y, Wu S - BMC Cancer (2015)

Downregulation of miR-490-3p in human CRC tissues and cell lines. a Global miRNA expression profile revealed miR-490-3p was downregulated in CRC tissues versus non-neoplastic colon. Each row of the heatmap indicated one tissue sample and each column indicated one miRNA. Labels in the right represented for miRNA symbol or probeset. Red: high expression; Green: low expression. b Quantitative real-time PCR analysis of miR-490-3p expression in 8 pairs of CRC tumor and adjacent non-tumor tissue samples. c Quantitative real-time PCR analysis of miR-490-3p expression in 8 CRC cell lines. *: A two-tailed t-test P-value <0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4696296&req=5

Fig1: Downregulation of miR-490-3p in human CRC tissues and cell lines. a Global miRNA expression profile revealed miR-490-3p was downregulated in CRC tissues versus non-neoplastic colon. Each row of the heatmap indicated one tissue sample and each column indicated one miRNA. Labels in the right represented for miRNA symbol or probeset. Red: high expression; Green: low expression. b Quantitative real-time PCR analysis of miR-490-3p expression in 8 pairs of CRC tumor and adjacent non-tumor tissue samples. c Quantitative real-time PCR analysis of miR-490-3p expression in 8 CRC cell lines. *: A two-tailed t-test P-value <0.05
Mentions: As described before, dual-faced functional roles of miR-490-3p have been found in various cancers, however, its correlation with CRC remains largely unknown, which prompt us to explore its expression and function in CRC. After data mining of previously reported global miRNA expression profiles of 54 cancerous and 20 non-cancerous colonic tissues [13], we identified a miRNA, miR-490-3p, was downregulated in majority of CRC samples (Fig. 1a). By quantitative real-time PCR determination, we confirmed the decreasing expression of miR-490-3p in 8 pairs of CRC tumor and adjacent non-tumor tissue samples (Fig. 1b), as well as in all the 8 CRC cell lines (HT29, SW620, SW480, HCT-15, LS174T, HCT116, LoVo, DLD-1) analyzed in this study (Fig. 1c, P < 0.05). Although wide expression discrepancies had been found among these patient samples and cell lines, individual heterogeneity and the complexity of clinical samples (including different tumor stage, tumor size, patient age and gender, and etc.) still do not mask this decreasing tendency. Moreover, miR-490-3p expression was further downregulated in fifteen metastasis CRC samples, in comparison with the expression level in fifteen matched non-metastasis CRC samples (Fig. 2a, P < 0.05). Following-up of these patients indicated lower expression level of miR-490-3p was associated with poor prognosis of survival (Fig. 2b, P < 0.05). Taken together, miR-490-3p expression was downregulated during CRC tumorigenesis and malignant progression. miR-490-3p perhaps acts as a tumor suppressor in CRC, which would be determined below.Fig. 1

Bottom Line: Artificially overexpression miR-490-3p in CRC cell lines inhibited cell migration and invasion abilities while knockdown miR-490-3p expression caused the reverse effects.Inhibition of TGFβR1 could partially recover the tumor suppression effect of miR-490-3p. miR-490-3p is downregulated during CRC malignant progression. miR-490-3p represses CRC cell migration and invasion abilities, partially by targeting to the TGF-β signaling pathway.Taken together, miR-490-3p is acting as a tumor suppressor in CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastrointestinal Surgery, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. xxh@gzhmu.edu.cn.

ABSTRACT

Background: Colorectal cancer (CRC) is one of the most common malignances worldwide. Metastasis is responsible for the rapid recurrence and poor prognosis of CRC. However, the underlying molecular mechanism of CRC metastasis remains largely unclear. In this study we purposed to investigate the expression and biological functions of miR-490-3p in CRC metastasis, as well as to identify its downstream target genes and influenced pathway.

Methods: The expression level of miR-490-3p in CRC cell lines, CRC adjacent normal tissues, non-metastasis and metastasis tissues were assessed by quantitative real-time PCR. Patient survivals were follow-up up to 7 years. Gain-of-function and loss-of-function study on cell migration and invasion abilities were carried out by transfection of miR-490-3p mimics or inhibitors respectively. The molecular targets of miR-490-3p were computationally identified and experimentally verified by dual-luciferase reporter assay and western blot. Functional rescue was also conducted to confirm miR-490-3p inhibits CRC metastasis by targeting TGF-β signaling pathway.

Results: miR-490-3p expression was persistently downregulated during CRC malignant progression, as well as in CRC cell lines. Artificially overexpression miR-490-3p in CRC cell lines inhibited cell migration and invasion abilities while knockdown miR-490-3p expression caused the reverse effects. TGFβR1 and MMP2/9 were the downstream targets of miR-490-3p in CRC. Inhibition of TGFβR1 could partially recover the tumor suppression effect of miR-490-3p.

Conclusion: miR-490-3p is downregulated during CRC malignant progression. miR-490-3p represses CRC cell migration and invasion abilities, partially by targeting to the TGF-β signaling pathway. Taken together, miR-490-3p is acting as a tumor suppressor in CRC.

No MeSH data available.


Related in: MedlinePlus