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. 2020 Feb 19;11(9):2716-2723.
doi: 10.7150/jca.34902. eCollection 2020.

MicroRNA-145 suppresses epithelial to mesenchymal transition in pancreatic cancer cells by inhibiting TGF-β signaling pathway

Shaojun Chen  1 , Junyi Xu  2 , Yao Su  3 , Li Hua  1 , Chengjun Feng  1 , Zhan Lin  4 , Haixin Huang  1 , Yongqiang Li  5
Affiliations

MicroRNA-145 suppresses epithelial to mesenchymal transition in pancreatic cancer cells by inhibiting TGF-β signaling pathway

Shaojun Chen et al. J Cancer. .

Abstract

TGF-β signaling plays a critical role in tumor progression and many approaches have been made to inhibit its functions. MicroRNA is one of the approaches that inhibit TGF-β signaling and can be used as a promising treatment for cancer. This study explored the role of miRNA-145 in pancreatic cancer (PC) development. The expression of miRNA-145 in PC tissues and paired adjacent normal tissues was examined by qRT-PCR. The expression of miRNA-145 in PC cells and the ability of cell migration and invasion were detected both in vivo and in vitro. The results showed that miRNA-145 was down-regulated in PC tissues and PC cells. Increasing the expression of miRNA-145 in PC cells inhibited the TGF-β signaling pathway and epithelial-mesenchymal transition (EMT) process. Scratch assay and transwell assay showed that miRNA-145 inhibited the migration and invasion in PC cells. In vivo experiments confirmed that miRNA-145 mimics delayed the growth of PC xenografts comparing with miRNA-145 inhibitor. Our results suggested that miRNA-145 can inhibit epithelial to mesenchymal transition (EMT) and tumor growth by suppressing TGF-β signaling pathway. Thus, miRNA-145 could be a potential therapeutic for targeting TGF-β signaling in PC treatment.

Keywords: EMT; TGF- β signaling; metastasis; miRNA-145; pancreatic cancer.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
MicroRNA-145 is down-regulated in PC tissues and cells. qRT-PCR on the expression of miRNA-145 in ( A): PC tissues and the paired adjacent normal tissues; (B): PC cells; and (C): PANC-1 and BxPC-3 cells transfected with mimic and inhibitor; D: MTT assay on the proliferation of PC cells after transfected with miRNA-145 mimic and inhibitor.
Figure 2
Figure 2
MicroRNA-145 inhibits TGF-β signaling pathway in PC cells. Western blotting. A: TGF- β expression after transfected with miRNA-145 mimic and inhibitor in PC cells; B: the expression of p-smad-2 in PC cells treated with different concentration of TGF- β; C: the expression of p-smad2 in PC cells transfected with miRNA-145 mimic and inhibitor.
Figure 3
Figure 3
MicroRNA-145 inhibits EMT in PC cells. A: Western blotting and B: qRT-PCR on the expression of epithelial and mesenchymal biomarkers in PC cells transfected with miRNA-145 mimic and inhibitor.
Figure 4
Figure 4
MicroRNA-145 inhibits cell migration and invasion in PC cells. Cell migration and invasion of PC cells transfected with miRNA-145 mimic and inhibitor examined by A: Scratch assay; B: Transwell assay; and C: Transwell assay with matrigel. D: The quantitative analysis of transwell assay; E: The quantitative analysis of transwell assay with Matrigel.
Figure 5
Figure 5
MicroRNA-145 inhibits pancreatic cancer metastasis in vivo.A: Tumor size of xenografts with PC cells transfected with miRNA-145 mimic and inhibitor; B: The Kaplan-Meier curve of xenograft with PC cells transfected with miRNA-145 mimic and inhibitor.
See this image and copyright information in PMC

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