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miR-126-3p Inhibits Thyroid Cancer Cell Growth and Metastasis, and Is Associated with Aggressive Thyroid Cancer.

Xiong Y, Kotian S, Zeiger MA, Zhang L, Kebebew E - PLoS ONE (2015)

Bottom Line: We found that miR-126-3p expression was significantly lower in larger tumors, in tumor samples with extrathyroidal invasion, and in higher risk group thyroid cancer in 496 papillary thyroid cancer samples from The Cancer Genome Atlas study cohort.In an independent sample set, lower miR-126-3p expression was observed in follicular thyroid cancers (which have capsular and angioinvasion) as compared to follicular adenomas.Of these 14 genes, SLC7A5 and ADAM9 were confirmed to be inhibited by miR-126-3p overexpression and to be direct targets of miR-136-3p.

View Article: PubMed Central - PubMed

Affiliation: Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.

ABSTRACT

Background: Previous studies have shown that microRNAs are dysregulated in thyroid cancer and play important roles in the post-transcriptional regulation of target oncogenes and/or tumor suppressor genes.

Methodology/principal findings: We studied the function of miR-126-3p in thyroid cancer cells, and as a marker of disease aggressiveness. We found that miR-126-3p expression was significantly lower in larger tumors, in tumor samples with extrathyroidal invasion, and in higher risk group thyroid cancer in 496 papillary thyroid cancer samples from The Cancer Genome Atlas study cohort. In an independent sample set, lower miR-126-3p expression was observed in follicular thyroid cancers (which have capsular and angioinvasion) as compared to follicular adenomas. Mechanistically, ectopic overexpression of miR-126-3p significantly inhibited thyroid cancer cell proliferation, in vitro (p<0.01) and in vivo (p<0.01), colony formation (p<0.01), tumor spheroid formation (p<0.05), cellular migration (p<0.05), VEGF secretion and endothelial tube formation, and lung metastasis in vivo. We found 14 predicted target genes, which were significantly altered upon miR-126-3p transfection in thyroid cancer cells, and which are involved in cancer biology. Of these 14 genes, SLC7A5 and ADAM9 were confirmed to be inhibited by miR-126-3p overexpression and to be direct targets of miR-136-3p.

Conclusions/significance: To our knowledge, this is the first study to demonstrate that miR-126-3p has a tumor-suppressive function in thyroid cancer cells, and is associated with aggressive disease phenotype.

No MeSH data available.


Related in: MedlinePlus

MiR-126-3p overexpression inhibits the migration of thyroid cancer cells.Wound healing assay (A) and Boyden chamber assay (B) data. MiR-126-3p overexpression significantly decreased wound width closure at 24 hours in all thyroid cancer cell lines studied. The Y axis represents the wound distance. Error bars represent SEM (** indicates p<0.01; *** indicates p<0.001). MiR-126-3p overexpression significantly decreased the number of migrated cells in all thyroid cancer cells in the Boyden chamber assay. The Y axis represents the number of migrated cells per field. Error bars represent SEM (* indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001).
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pone.0130496.g003: MiR-126-3p overexpression inhibits the migration of thyroid cancer cells.Wound healing assay (A) and Boyden chamber assay (B) data. MiR-126-3p overexpression significantly decreased wound width closure at 24 hours in all thyroid cancer cell lines studied. The Y axis represents the wound distance. Error bars represent SEM (** indicates p<0.01; *** indicates p<0.001). MiR-126-3p overexpression significantly decreased the number of migrated cells in all thyroid cancer cells in the Boyden chamber assay. The Y axis represents the number of migrated cells per field. Error bars represent SEM (* indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001).

Mentions: We next determined the effect of miR-126-3p on cellular migration using the scratch wound healing assay. We found that overexpression of miR-126-3p significantly inhibited wound closure in TPC-1 cells (p<0.001), FTC-133 cells (p<0.001), and XTC-1 cells (p<0.01) (Fig 3A). To confirm our findings, we also used a Boyden chamber assay to study the effect of miR-126-3p on cellular migration. We found that overexpression of miR-126-3p also significantly inhibited cell migration (Fig 3B).


miR-126-3p Inhibits Thyroid Cancer Cell Growth and Metastasis, and Is Associated with Aggressive Thyroid Cancer.

Xiong Y, Kotian S, Zeiger MA, Zhang L, Kebebew E - PLoS ONE (2015)

MiR-126-3p overexpression inhibits the migration of thyroid cancer cells.Wound healing assay (A) and Boyden chamber assay (B) data. MiR-126-3p overexpression significantly decreased wound width closure at 24 hours in all thyroid cancer cell lines studied. The Y axis represents the wound distance. Error bars represent SEM (** indicates p<0.01; *** indicates p<0.001). MiR-126-3p overexpression significantly decreased the number of migrated cells in all thyroid cancer cells in the Boyden chamber assay. The Y axis represents the number of migrated cells per field. Error bars represent SEM (* indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4526518&req=5

pone.0130496.g003: MiR-126-3p overexpression inhibits the migration of thyroid cancer cells.Wound healing assay (A) and Boyden chamber assay (B) data. MiR-126-3p overexpression significantly decreased wound width closure at 24 hours in all thyroid cancer cell lines studied. The Y axis represents the wound distance. Error bars represent SEM (** indicates p<0.01; *** indicates p<0.001). MiR-126-3p overexpression significantly decreased the number of migrated cells in all thyroid cancer cells in the Boyden chamber assay. The Y axis represents the number of migrated cells per field. Error bars represent SEM (* indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001).
Mentions: We next determined the effect of miR-126-3p on cellular migration using the scratch wound healing assay. We found that overexpression of miR-126-3p significantly inhibited wound closure in TPC-1 cells (p<0.001), FTC-133 cells (p<0.001), and XTC-1 cells (p<0.01) (Fig 3A). To confirm our findings, we also used a Boyden chamber assay to study the effect of miR-126-3p on cellular migration. We found that overexpression of miR-126-3p also significantly inhibited cell migration (Fig 3B).

Bottom Line: We found that miR-126-3p expression was significantly lower in larger tumors, in tumor samples with extrathyroidal invasion, and in higher risk group thyroid cancer in 496 papillary thyroid cancer samples from The Cancer Genome Atlas study cohort.In an independent sample set, lower miR-126-3p expression was observed in follicular thyroid cancers (which have capsular and angioinvasion) as compared to follicular adenomas.Of these 14 genes, SLC7A5 and ADAM9 were confirmed to be inhibited by miR-126-3p overexpression and to be direct targets of miR-136-3p.

View Article: PubMed Central - PubMed

Affiliation: Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.

ABSTRACT

Background: Previous studies have shown that microRNAs are dysregulated in thyroid cancer and play important roles in the post-transcriptional regulation of target oncogenes and/or tumor suppressor genes.

Methodology/principal findings: We studied the function of miR-126-3p in thyroid cancer cells, and as a marker of disease aggressiveness. We found that miR-126-3p expression was significantly lower in larger tumors, in tumor samples with extrathyroidal invasion, and in higher risk group thyroid cancer in 496 papillary thyroid cancer samples from The Cancer Genome Atlas study cohort. In an independent sample set, lower miR-126-3p expression was observed in follicular thyroid cancers (which have capsular and angioinvasion) as compared to follicular adenomas. Mechanistically, ectopic overexpression of miR-126-3p significantly inhibited thyroid cancer cell proliferation, in vitro (p<0.01) and in vivo (p<0.01), colony formation (p<0.01), tumor spheroid formation (p<0.05), cellular migration (p<0.05), VEGF secretion and endothelial tube formation, and lung metastasis in vivo. We found 14 predicted target genes, which were significantly altered upon miR-126-3p transfection in thyroid cancer cells, and which are involved in cancer biology. Of these 14 genes, SLC7A5 and ADAM9 were confirmed to be inhibited by miR-126-3p overexpression and to be direct targets of miR-136-3p.

Conclusions/significance: To our knowledge, this is the first study to demonstrate that miR-126-3p has a tumor-suppressive function in thyroid cancer cells, and is associated with aggressive disease phenotype.

No MeSH data available.


Related in: MedlinePlus