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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 inhibits cell proliferation in NSCLC cells.(a) qPCR analysis to quantify the expression levels of miR-181b in HBE, A549/DDP, A549 and H1650 cell lines. U6 was used for normalization. (b) CCK analysis of cell proliferation after transfected with miR-181b mimics, miR-181b inhibitors, or control in A549/DDP or A549 cell lines. (c) Colony-forming efficiency was detected in A549/DDP or A549 cell lines transfected with the miR-181b mimics or miR-181b inhibitors. *P < 0.05; **P < 0.01.
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f1: MiR-181b inhibits cell proliferation in NSCLC cells.(a) qPCR analysis to quantify the expression levels of miR-181b in HBE, A549/DDP, A549 and H1650 cell lines. U6 was used for normalization. (b) CCK analysis of cell proliferation after transfected with miR-181b mimics, miR-181b inhibitors, or control in A549/DDP or A549 cell lines. (c) Colony-forming efficiency was detected in A549/DDP or A549 cell lines transfected with the miR-181b mimics or miR-181b inhibitors. *P < 0.05; **P < 0.01.

Mentions: In this study, we investigated the expression levels of miR-181b in HBE normal lung epithelial cell line, A549, H1650 and A549/DDP lung cancer cell lines. MiR-181b expression was significantly decreased in A549/DDP cells compared with A549 and H1650 cells, and they were lower than HBE normal lung epithelial cells, as detected by qPCR (Fig. 1a).


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 inhibits cell proliferation in NSCLC cells.(a) qPCR analysis to quantify the expression levels of miR-181b in HBE, A549/DDP, A549 and H1650 cell lines. U6 was used for normalization. (b) CCK analysis of cell proliferation after transfected with miR-181b mimics, miR-181b inhibitors, or control in A549/DDP or A549 cell lines. (c) Colony-forming efficiency was detected in A549/DDP or A549 cell lines transfected with the miR-181b mimics or miR-181b inhibitors. *P < 0.05; **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: MiR-181b inhibits cell proliferation in NSCLC cells.(a) qPCR analysis to quantify the expression levels of miR-181b in HBE, A549/DDP, A549 and H1650 cell lines. U6 was used for normalization. (b) CCK analysis of cell proliferation after transfected with miR-181b mimics, miR-181b inhibitors, or control in A549/DDP or A549 cell lines. (c) Colony-forming efficiency was detected in A549/DDP or A549 cell lines transfected with the miR-181b mimics or miR-181b inhibitors. *P < 0.05; **P < 0.01.
Mentions: In this study, we investigated the expression levels of miR-181b in HBE normal lung epithelial cell line, A549, H1650 and A549/DDP lung cancer cell lines. MiR-181b expression was significantly decreased in A549/DDP cells compared with A549 and H1650 cells, and they were lower than HBE normal lung epithelial cells, as detected by qPCR (Fig. 1a).

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