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Weiming Hu
Sichuan University West China Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4943-8412
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Background: Pancreatic cancer is one of the leading causes of cancer deaths, with high chance of metastasis associated with high mortality rates. Epithelial-to-mesenchymal transition (EMT) is one of the crucial steps in the initiation of metastasis, when cells begin to lose adhesion and gain invasive properties. Transforming growth factor beta (TGF-β) is known to promote EMT via binding to its receptors, TGFBR1 and TGFBR2, which are overexpressed in pancreatic cancer cells.
Methods: The expression of MALAT1 was detected in pancreatic cancer tissues. The dual-luciferase assay was performed to validate the binding between MALAT1 and miR-141-5p. The western blot was performed to detect the expression of both TGFBR1 and TGFBR2.
Results: The long noncoding RNA (lncRNA) MALAT1 is highly expressed in cancer cells and positively correlated with tumor growth and metastasis. Our study revealed that MALAT1 suppresses the expression of miR-141-5p by acting as a “miRNA sponge”. We validated the sequence-specific binding between MALAT1 and miR-141-5p by dual-luciferase experiment, and found that their expressions are negatively correlated in pancreatic cancer cells. Furthermore, miR-141-5p downregulates TGFBR1 and TGFBR2, and reduces cell migration and invasion that are caused by TGF-β-induced EMT. However, the overexpression of MALAT1 in pancreatic cancer cells suppresses the expression of miR-141-5p. Underexpression of miR-141-5p promotes the expression of TGFBR1 and TGFBR2, inducing EMT through the TGF-β pathway.
Conclusions: The overexpression of MALAT1 is a key component in initiating metastasis in pancreatic cancer, by inhibiting the effect of miR-141-5p and promoting TGF-β-induced EMT.
Keywords
pancreatic cancer, epithelial-to-mesenchymal transition, EMT, TGF-β, MALAT1, miR-141-5p, TGFBR
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Weiming Hu
Sichuan University West China Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4943-8412
Badges
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Complete author information
Appropriate declaration statements
Potential risks to human health
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History
CURRENT STATUS: Posted
The most recent version of this article is available here.
No community comments so far
Version 1
Posted 25 Aug, 2020
No comments provided
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Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
Background: Pancreatic cancer is one of the leading causes of cancer deaths, with high chance of metastasis associated with high mortality rates. Epithelial-to-mesenchymal transition (EMT) is one of the crucial steps in the initiation of metastasis, when cells begin to lose adhesion and gain invasive properties. Transforming growth factor beta (TGF-β) is known to promote EMT via binding to its receptors, TGFBR1 and TGFBR2, which are overexpressed in pancreatic cancer cells.
Methods: The expression of MALAT1 was detected in pancreatic cancer tissues. The dual-luciferase assay was performed to validate the binding between MALAT1 and miR-141-5p. The western blot was performed to detect the expression of both TGFBR1 and TGFBR2.
Results: The long noncoding RNA (lncRNA) MALAT1 is highly expressed in cancer cells and positively correlated with tumor growth and metastasis. Our study revealed that MALAT1 suppresses the expression of miR-141-5p by acting as a “miRNA sponge”. We validated the sequence-specific binding between MALAT1 and miR-141-5p by dual-luciferase experiment, and found that their expressions are negatively correlated in pancreatic cancer cells. Furthermore, miR-141-5p downregulates TGFBR1 and TGFBR2, and reduces cell migration and invasion that are caused by TGF-β-induced EMT. However, the overexpression of MALAT1 in pancreatic cancer cells suppresses the expression of miR-141-5p. Underexpression of miR-141-5p promotes the expression of TGFBR1 and TGFBR2, inducing EMT through the TGF-β pathway.
Conclusions: The overexpression of MALAT1 is a key component in initiating metastasis in pancreatic cancer, by inhibiting the effect of miR-141-5p and promoting TGF-β-induced EMT.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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