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Trail resistance induces epithelial-mesenchymal transition and enhances invasiveness by suppressing PTEN via miR-221 in breast cancer.

Wang H, Xu C, Kong X, Li X, Kong X, Wang Y, Ding X, Yang Q - PLoS ONE (2014)

Bottom Line: In our present experiment, we successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL-resistant cell line.We found resistance to TRAIL could induce epithelial-mesenchymal transition (EMT) and enhance invasiveness.Re-expression of miR-221 or targeting PTEN might serve as potential therapeutic approaches for the treatment of Trail-resistant breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China; Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.

ABSTRACT
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis of cancer cells and is verified effective to various cancers. However, a variety of breast cancer cell lines are resistant to TRAIL and the mechanisms of resistance are largely unknown. In our present experiment, we successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL-resistant cell line. We found resistance to TRAIL could induce epithelial-mesenchymal transition (EMT) and enhance invasiveness. We further demonstrated PTEN was down-regulated in TRAIL-resistant cells. Silencing miR-221, PTEN expression was up-regulated, the process of EMT could be reversed, and the ability of migration and invasion were correspondingly weakened. We also demonstrated knockdown of miR-221 could reverse resistance to TRAIL partially by targeting PTEN. Our findings suggest that resistance to TRAIL could induce EMT and enhance invasiveness by suppressing PTEN via miR-221. Re-expression of miR-221 or targeting PTEN might serve as potential therapeutic approaches for the treatment of Trail-resistant breast cancer.

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Related in: MedlinePlus

MiR-21 was over-expressed in 231T cells but not the key regulator in TRAIL-resistance.A. Several miRNAs were detected in 231 and 231T cells. miR-21 and miR-221 were statistically up-regulated in 231T cells. B. miR-21 was silenced by inhibitor in 231T cells. C. Silence of miR-21 didn't reverse the resistance of 231T cells measured by MTT assay. D. After silencing miR-21, expression of PTEN didn't change. *P<0.05; **P<0.01.
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pone-0099067-g005: MiR-21 was over-expressed in 231T cells but not the key regulator in TRAIL-resistance.A. Several miRNAs were detected in 231 and 231T cells. miR-21 and miR-221 were statistically up-regulated in 231T cells. B. miR-21 was silenced by inhibitor in 231T cells. C. Silence of miR-21 didn't reverse the resistance of 231T cells measured by MTT assay. D. After silencing miR-21, expression of PTEN didn't change. *P<0.05; **P<0.01.

Mentions: In order to explore the regulator of PTEN, we detected miR-21, miR-221, miR-222, miR-23b-3p and miR-214 expression based on data mining and miRNA prediction. The expression of miR-23b-3p and miR-214 was not different between 231 cells and 231T cells. We found that miR-21 was over-expressed obviously in 231T cells, about 140 times compared with 231 cells, which is the highest of the miRNAs we detected (Figure 5A). Then we inhibited miR-21 in 231T cells (Figure 5B), but the cells were not turn to be sensitive to TRAIL (Figure 5C). Furthermore, the expression of PTEN was equal to 231T cells (Figure 5D). Therefore, we infer that miR-21 was not the key regulator of PTEN and it was not related with TRAIL-resistance.


Trail resistance induces epithelial-mesenchymal transition and enhances invasiveness by suppressing PTEN via miR-221 in breast cancer.

Wang H, Xu C, Kong X, Li X, Kong X, Wang Y, Ding X, Yang Q - PLoS ONE (2014)

MiR-21 was over-expressed in 231T cells but not the key regulator in TRAIL-resistance.A. Several miRNAs were detected in 231 and 231T cells. miR-21 and miR-221 were statistically up-regulated in 231T cells. B. miR-21 was silenced by inhibitor in 231T cells. C. Silence of miR-21 didn't reverse the resistance of 231T cells measured by MTT assay. D. After silencing miR-21, expression of PTEN didn't change. *P<0.05; **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048247&req=5

pone-0099067-g005: MiR-21 was over-expressed in 231T cells but not the key regulator in TRAIL-resistance.A. Several miRNAs were detected in 231 and 231T cells. miR-21 and miR-221 were statistically up-regulated in 231T cells. B. miR-21 was silenced by inhibitor in 231T cells. C. Silence of miR-21 didn't reverse the resistance of 231T cells measured by MTT assay. D. After silencing miR-21, expression of PTEN didn't change. *P<0.05; **P<0.01.
Mentions: In order to explore the regulator of PTEN, we detected miR-21, miR-221, miR-222, miR-23b-3p and miR-214 expression based on data mining and miRNA prediction. The expression of miR-23b-3p and miR-214 was not different between 231 cells and 231T cells. We found that miR-21 was over-expressed obviously in 231T cells, about 140 times compared with 231 cells, which is the highest of the miRNAs we detected (Figure 5A). Then we inhibited miR-21 in 231T cells (Figure 5B), but the cells were not turn to be sensitive to TRAIL (Figure 5C). Furthermore, the expression of PTEN was equal to 231T cells (Figure 5D). Therefore, we infer that miR-21 was not the key regulator of PTEN and it was not related with TRAIL-resistance.

Bottom Line: In our present experiment, we successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL-resistant cell line.We found resistance to TRAIL could induce epithelial-mesenchymal transition (EMT) and enhance invasiveness.Re-expression of miR-221 or targeting PTEN might serve as potential therapeutic approaches for the treatment of Trail-resistant breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China; Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.

ABSTRACT
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis of cancer cells and is verified effective to various cancers. However, a variety of breast cancer cell lines are resistant to TRAIL and the mechanisms of resistance are largely unknown. In our present experiment, we successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL-resistant cell line. We found resistance to TRAIL could induce epithelial-mesenchymal transition (EMT) and enhance invasiveness. We further demonstrated PTEN was down-regulated in TRAIL-resistant cells. Silencing miR-221, PTEN expression was up-regulated, the process of EMT could be reversed, and the ability of migration and invasion were correspondingly weakened. We also demonstrated knockdown of miR-221 could reverse resistance to TRAIL partially by targeting PTEN. Our findings suggest that resistance to TRAIL could induce EMT and enhance invasiveness by suppressing PTEN via miR-221. Re-expression of miR-221 or targeting PTEN might serve as potential therapeutic approaches for the treatment of Trail-resistant breast cancer.

Show MeSH
Related in: MedlinePlus