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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

Inhibition of TGFβR1 partially recovers the tumor suppression function of miR-490-3p. a CRC cells (LS174T and HCT116) were treated with TGFβR1 siRNA, miR-490-3p inhibitors, or both of them. Western blot presented the TGFβR1 protein level after interference. b Cell migration ability was assessed by transwell matrix penetration assay after interference. Co-transfection of TGFβR1 siRNA and miR-490-3p inhibitors partially but not completely reduced the malignant potency caused by miR-490-3p inhibitors. *: A two-tailed t-test P-value <0.05
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Fig6: Inhibition of TGFβR1 partially recovers the tumor suppression function of miR-490-3p. a CRC cells (LS174T and HCT116) were treated with TGFβR1 siRNA, miR-490-3p inhibitors, or both of them. Western blot presented the TGFβR1 protein level after interference. b Cell migration ability was assessed by transwell matrix penetration assay after interference. Co-transfection of TGFβR1 siRNA and miR-490-3p inhibitors partially but not completely reduced the malignant potency caused by miR-490-3p inhibitors. *: A two-tailed t-test P-value <0.05

Mentions: To further investigate the functional consequence of the miR-490-3p/TGFβR1 interactions in CRC, we compared the migration abilities of CRC cells treated with TGFβR1 siRNA, miR-490-3p inhibitors, or both of them. TGFβR1 siRNA markedly reduced the TGFβR1 protein level, while miR-490-3p inhibitors elevated the TGFβR1 protein level. Co-transfection of TGFβR1 siRNA and miR-490-3p inhibitors partially recovered TGFβR1 expression when compared to the cells only transfected with siRNA (Fig. 6a). Meanwhile, the cell migration ability was assessed by transwell matrix penetration assay for the same treatment. Transfection of TGFβR1 siRNA decreased the migrated cells and transfection of miR-490-3p inhibitors increased the migrated cells respectively. Co-transfection of them partially but not completely reduced the malignant potency caused by miR-490-3p inhibitors (Fig. 6b). Taken together, evidences indicated inhibition of TGFβR1 could partially recover the tumor suppression effect of miR-490-3p.Fig. 6


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)

Inhibition of TGFβR1 partially recovers the tumor suppression function of miR-490-3p. a CRC cells (LS174T and HCT116) were treated with TGFβR1 siRNA, miR-490-3p inhibitors, or both of them. Western blot presented the TGFβR1 protein level after interference. b Cell migration ability was assessed by transwell matrix penetration assay after interference. Co-transfection of TGFβR1 siRNA and miR-490-3p inhibitors partially but not completely reduced the malignant potency caused by miR-490-3p inhibitors. *: 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

Fig6: Inhibition of TGFβR1 partially recovers the tumor suppression function of miR-490-3p. a CRC cells (LS174T and HCT116) were treated with TGFβR1 siRNA, miR-490-3p inhibitors, or both of them. Western blot presented the TGFβR1 protein level after interference. b Cell migration ability was assessed by transwell matrix penetration assay after interference. Co-transfection of TGFβR1 siRNA and miR-490-3p inhibitors partially but not completely reduced the malignant potency caused by miR-490-3p inhibitors. *: A two-tailed t-test P-value <0.05
Mentions: To further investigate the functional consequence of the miR-490-3p/TGFβR1 interactions in CRC, we compared the migration abilities of CRC cells treated with TGFβR1 siRNA, miR-490-3p inhibitors, or both of them. TGFβR1 siRNA markedly reduced the TGFβR1 protein level, while miR-490-3p inhibitors elevated the TGFβR1 protein level. Co-transfection of TGFβR1 siRNA and miR-490-3p inhibitors partially recovered TGFβR1 expression when compared to the cells only transfected with siRNA (Fig. 6a). Meanwhile, the cell migration ability was assessed by transwell matrix penetration assay for the same treatment. Transfection of TGFβR1 siRNA decreased the migrated cells and transfection of miR-490-3p inhibitors increased the migrated cells respectively. Co-transfection of them partially but not completely reduced the malignant potency caused by miR-490-3p inhibitors (Fig. 6b). Taken together, evidences indicated inhibition of TGFβR1 could partially recover the tumor suppression effect of miR-490-3p.Fig. 6

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