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MiR-181b regulates cisplatin chemosensitivity and metastasis by targeting TGFβR1/Smad signaling pathway in NSCLC.

Wang X, Chen X, Meng Q, Jing H, Lu H, Yang Y, Cai L, Zhao Y - Sci Rep (2015)

Bottom Line: We found that miR-181b expression levels were lower in A549/DDP cells compared with A549 cells.In addition, miR-181b could inactivate the TGFβR1/Smad signaling pathway.We also observed that decreased miR-181b expression and increased TGFβR1 expression were significantly associated with chemosensitivity to DDP and tumor metastasis in NSCLC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medical Oncology, Harbin medical University Cancer Hospital, Harbin, Heilongjiang Province, China.

ABSTRACT
MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells, but their underlying mechanisms in chemosensitivity and metastasis have not been fully elucidated. The objective of this study was to identify miR-181b and its mechanism in the chemosensitivity and metastasis of NSCLC. We found that miR-181b expression levels were lower in A549/DDP cells compared with A549 cells. Functional assays showed that the overexpression of miR-181b inhibited proliferation, enhanced chemosensitivity to DDP, attenuated migration and metastatic ability in NSCLC cell lines in vitro and in vivo. TGFβR1 was subsequently identified as a novel functional target of miR-181b. TGFβR1 knockdown revealed similar effects as that of ectopic miR-181b expression, whereas overexpression of TGFβR1 rescued the function of miR-181b-mediated growth, chemosensitivity and metastasis in NSCLC cells. In addition, miR-181b could inactivate the TGFβR1/Smad signaling pathway. We also observed that decreased miR-181b expression and increased TGFβR1 expression were significantly associated with chemosensitivity to DDP and tumor metastasis in NSCLC patients. Consequently, miR-181b functions as a tumor suppressor and has an important role in proliferation, chemosensitivity to DDP and metastasis of NSCLC by targeting TGFβR1/Smad signaling pathway.

No MeSH data available.


Related in: MedlinePlus

MiR-181b enhances chemosensitivity of NSCLC cells to DDP.(a) CCK analysis of IC50 values of DDP after transfected with miR-181b mimics, miR-181b inhibitors, or control in A549/DDP or A549 cell lines. (b) Flow cytometric analysis of cell cycle in A549/DDP and A549 were determined after transfected miR-181b mimics, miR-controls, miR-181b inhibitors or negative controls combined with DDP. (c) Flow cytometric analysis of apoptosis in A549/DDP and A549 were determined after transfected miR-181b mimics, miR controls, miR-181b inhibitors or negative controls combined with DDP. *P < 0.05; **P < 0.01; ***P < 0.001.
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f2: MiR-181b enhances chemosensitivity of NSCLC cells to DDP.(a) CCK analysis of IC50 values of DDP after transfected with miR-181b mimics, miR-181b inhibitors, or control in A549/DDP or A549 cell lines. (b) Flow cytometric analysis of cell cycle in A549/DDP and A549 were determined after transfected miR-181b mimics, miR-controls, miR-181b inhibitors or negative controls combined with DDP. (c) Flow cytometric analysis of apoptosis in A549/DDP and A549 were determined after transfected miR-181b mimics, miR controls, miR-181b inhibitors or negative controls combined with DDP. *P < 0.05; **P < 0.01; ***P < 0.001.

Mentions: Next, we assessed the functional role of miR-181b in chemosensitivity of NSCLC cells to DDP. After transfected with miR-181b mimics, the IC50 of A549/DDP cells to DDP was significantly decreased (313.80 ± 17.21 umol/l vs 89.35 ± 3.38 umol/l, P < 0.01), as evidenced by the growth inhibition curve. Conversely, inhibition of miR-181b could simultaneously protected A549 and H1650 cells from cisplatin treatment (P <  0.001, Fig. 2a and Fig. S2a).


MiR-181b regulates cisplatin chemosensitivity and metastasis by targeting TGFβR1/Smad signaling pathway in NSCLC.

Wang X, Chen X, Meng Q, Jing H, Lu H, Yang Y, Cai L, Zhao Y - Sci Rep (2015)

MiR-181b enhances chemosensitivity of NSCLC cells to DDP.(a) CCK analysis of IC50 values of DDP after transfected with miR-181b mimics, miR-181b inhibitors, or control in A549/DDP or A549 cell lines. (b) Flow cytometric analysis of cell cycle in A549/DDP and A549 were determined after transfected miR-181b mimics, miR-controls, miR-181b inhibitors or negative controls combined with DDP. (c) Flow cytometric analysis of apoptosis in A549/DDP and A549 were determined after transfected miR-181b mimics, miR controls, miR-181b inhibitors or negative controls combined with DDP. *P < 0.05; **P < 0.01; ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664936&req=5

f2: MiR-181b enhances chemosensitivity of NSCLC cells to DDP.(a) CCK analysis of IC50 values of DDP after transfected with miR-181b mimics, miR-181b inhibitors, or control in A549/DDP or A549 cell lines. (b) Flow cytometric analysis of cell cycle in A549/DDP and A549 were determined after transfected miR-181b mimics, miR-controls, miR-181b inhibitors or negative controls combined with DDP. (c) Flow cytometric analysis of apoptosis in A549/DDP and A549 were determined after transfected miR-181b mimics, miR controls, miR-181b inhibitors or negative controls combined with DDP. *P < 0.05; **P < 0.01; ***P < 0.001.
Mentions: Next, we assessed the functional role of miR-181b in chemosensitivity of NSCLC cells to DDP. After transfected with miR-181b mimics, the IC50 of A549/DDP cells to DDP was significantly decreased (313.80 ± 17.21 umol/l vs 89.35 ± 3.38 umol/l, P < 0.01), as evidenced by the growth inhibition curve. Conversely, inhibition of miR-181b could simultaneously protected A549 and H1650 cells from cisplatin treatment (P <  0.001, Fig. 2a and Fig. S2a).

Bottom Line: We found that miR-181b expression levels were lower in A549/DDP cells compared with A549 cells.In addition, miR-181b could inactivate the TGFβR1/Smad signaling pathway.We also observed that decreased miR-181b expression and increased TGFβR1 expression were significantly associated with chemosensitivity to DDP and tumor metastasis in NSCLC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medical Oncology, Harbin medical University Cancer Hospital, Harbin, Heilongjiang Province, China.

ABSTRACT
MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells, but their underlying mechanisms in chemosensitivity and metastasis have not been fully elucidated. The objective of this study was to identify miR-181b and its mechanism in the chemosensitivity and metastasis of NSCLC. We found that miR-181b expression levels were lower in A549/DDP cells compared with A549 cells. Functional assays showed that the overexpression of miR-181b inhibited proliferation, enhanced chemosensitivity to DDP, attenuated migration and metastatic ability in NSCLC cell lines in vitro and in vivo. TGFβR1 was subsequently identified as a novel functional target of miR-181b. TGFβR1 knockdown revealed similar effects as that of ectopic miR-181b expression, whereas overexpression of TGFβR1 rescued the function of miR-181b-mediated growth, chemosensitivity and metastasis in NSCLC cells. In addition, miR-181b could inactivate the TGFβR1/Smad signaling pathway. We also observed that decreased miR-181b expression and increased TGFβR1 expression were significantly associated with chemosensitivity to DDP and tumor metastasis in NSCLC patients. Consequently, miR-181b functions as a tumor suppressor and has an important role in proliferation, chemosensitivity to DDP and metastasis of NSCLC by targeting TGFβR1/Smad signaling pathway.

No MeSH data available.


Related in: MedlinePlus