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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

Knockdown of miR-490-3p promotes CRC cell migration and invasion. a Wound healing assay was used to assess the mobile ability of CRC cells (LS174T and HCT116) transfected with miR-490-3p inhibitors or negative control respectively. Knockdown of miR-490-3p expression markedly accelerated the wound healing (magnification: 100x). b Transwell matrix penetration assay revealed knockdown of miR-490-3p expression significantly increased the number of invaded CRC cells (P < 0.05). c Cell 3D morphology showed that LS174T and HCT116 CRC cells with decreased expression of miR-490-3p presented more outward projections and irregular shapes, which was associated with an highly aggressive ability (magnification: 200x). *: A two-tailed t-test P-value <0.05
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Fig4: Knockdown of miR-490-3p promotes CRC cell migration and invasion. a Wound healing assay was used to assess the mobile ability of CRC cells (LS174T and HCT116) transfected with miR-490-3p inhibitors or negative control respectively. Knockdown of miR-490-3p expression markedly accelerated the wound healing (magnification: 100x). b Transwell matrix penetration assay revealed knockdown of miR-490-3p expression significantly increased the number of invaded CRC cells (P < 0.05). c Cell 3D morphology showed that LS174T and HCT116 CRC cells with decreased expression of miR-490-3p presented more outward projections and irregular shapes, which was associated with an highly aggressive ability (magnification: 200x). *: A two-tailed t-test P-value <0.05

Mentions: By wound healing assay, we found that overexpression of miR-490-3p slowed down the confluence of LS174T and HCT116 cells (Fig. 3a), while knockdown of miR-490-3p promoted the wounds healing reversely (Fig. 4a). Similar effects were observed in Matrigel transwell assay. Overexpression of miR-490-3p dramatically reduced the number of invaded cells on the membrane bottom-surface (Fig. 3b, P < 0.05) and knockdown of miR-490-3p increased the number of invaded cells (Fig. 4b, P < 0.05). All the above observations suggested miR-490-3p could suppress CRC cell migration and invasion abilities.Fig. 3


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)

Knockdown of miR-490-3p promotes CRC cell migration and invasion. a Wound healing assay was used to assess the mobile ability of CRC cells (LS174T and HCT116) transfected with miR-490-3p inhibitors or negative control respectively. Knockdown of miR-490-3p expression markedly accelerated the wound healing (magnification: 100x). b Transwell matrix penetration assay revealed knockdown of miR-490-3p expression significantly increased the number of invaded CRC cells (P < 0.05). c Cell 3D morphology showed that LS174T and HCT116 CRC cells with decreased expression of miR-490-3p presented more outward projections and irregular shapes, which was associated with an highly aggressive ability (magnification: 200x). *: 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

Fig4: Knockdown of miR-490-3p promotes CRC cell migration and invasion. a Wound healing assay was used to assess the mobile ability of CRC cells (LS174T and HCT116) transfected with miR-490-3p inhibitors or negative control respectively. Knockdown of miR-490-3p expression markedly accelerated the wound healing (magnification: 100x). b Transwell matrix penetration assay revealed knockdown of miR-490-3p expression significantly increased the number of invaded CRC cells (P < 0.05). c Cell 3D morphology showed that LS174T and HCT116 CRC cells with decreased expression of miR-490-3p presented more outward projections and irregular shapes, which was associated with an highly aggressive ability (magnification: 200x). *: A two-tailed t-test P-value <0.05
Mentions: By wound healing assay, we found that overexpression of miR-490-3p slowed down the confluence of LS174T and HCT116 cells (Fig. 3a), while knockdown of miR-490-3p promoted the wounds healing reversely (Fig. 4a). Similar effects were observed in Matrigel transwell assay. Overexpression of miR-490-3p dramatically reduced the number of invaded cells on the membrane bottom-surface (Fig. 3b, P < 0.05) and knockdown of miR-490-3p increased the number of invaded cells (Fig. 4b, P < 0.05). All the above observations suggested miR-490-3p could suppress CRC cell migration and invasion abilities.Fig. 3

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