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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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PTEN was the target gene of miR-221.A. miR-221 was predicted to regulate PTEN. B. After silencing miR-221, the mRNA level of PTEN was significantly up-regulated detected by real-time PCR. C. The corresponding change of PTEN in 231T-n and 231T-si221 cells was detected by western blot assay. *P<0.05; **P<0.01.
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pone-0099067-g006: PTEN was the target gene of miR-221.A. miR-221 was predicted to regulate PTEN. B. After silencing miR-221, the mRNA level of PTEN was significantly up-regulated detected by real-time PCR. C. The corresponding change of PTEN in 231T-n and 231T-si221 cells was detected by western blot assay. *P<0.05; **P<0.01.

Mentions: We further analyzed miR-221, another PTEN possible regulator (Figure 6A). In 231T cells, miR-221 was over-expressed, which was over 90 times in contrast with 231 cells, next only to miR-21(Figure 5A). Since miR-21 might not be the key regulator of TRAIL-resistance, we performed knockdown of miR-221 in 231T cells by transfection (231T-si221), and confirmed the efficiency of transfection by real-time RT-PCR contrasting with cells transfected with negative control (231T-n). After transfection, the mRNA level and protein level of PTEN were both significantly up-regulated (p<0.05) (Figure 6B and C). These data indicated that resistance to TRAIL could induce the up-regulation of miR-221 and PTEN might be the target gene of miR-221.


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)

PTEN was the target gene of miR-221.A. miR-221 was predicted to regulate PTEN. B. After silencing miR-221, the mRNA level of PTEN was significantly up-regulated detected by real-time PCR. C. The corresponding change of PTEN in 231T-n and 231T-si221 cells was detected by western blot assay. *P<0.05; **P<0.01.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4048247&req=5

pone-0099067-g006: PTEN was the target gene of miR-221.A. miR-221 was predicted to regulate PTEN. B. After silencing miR-221, the mRNA level of PTEN was significantly up-regulated detected by real-time PCR. C. The corresponding change of PTEN in 231T-n and 231T-si221 cells was detected by western blot assay. *P<0.05; **P<0.01.
Mentions: We further analyzed miR-221, another PTEN possible regulator (Figure 6A). In 231T cells, miR-221 was over-expressed, which was over 90 times in contrast with 231 cells, next only to miR-21(Figure 5A). Since miR-21 might not be the key regulator of TRAIL-resistance, we performed knockdown of miR-221 in 231T cells by transfection (231T-si221), and confirmed the efficiency of transfection by real-time RT-PCR contrasting with cells transfected with negative control (231T-n). After transfection, the mRNA level and protein level of PTEN were both significantly up-regulated (p<0.05) (Figure 6B and C). These data indicated that resistance to TRAIL could induce the up-regulation of miR-221 and PTEN might be the target gene of miR-221.

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