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ABSTRACT
Background
Transmembrane-4-L-six-family-1 (TM4SF1) functions to regulate cell growth and mobility and TM4SF1 expression was upregulated in pancreatic cancer. This study further investigated the role of TM4SF1 in regulating pancreatic cancer epithelial-mesenchymal transition (EMT) and angiogenesis and the underlying molecular events.
Methods
Tissue specimens were collected from 90 pancreatic cancer patients for immunohistochemical and qRT-PCR analysis of miR-141 and TM4SF1 levels, respectively. Pancreatic cancer cell lines were used for in vitro assays, while nude mice were used for the in vivo assay.
Results
TM4SF1 expression was upregulated, whereas miR-141 expression was lost in pancreatic cancer tissues, both of which was associated with advanced clinicopathological features and poor survival of pancreatic cancer patients. Furthermore, miR-141 was able to target and reduce TM4SF1 expression in pancreatic cancer cells and miR-141 expression inhibited pancreatic cancer cell EMT in vitro and Matrigel plug angiogenesis and lung metastasis in nude mice. At the gene level, miR-141 directly targeted and reduced TM4SF1 expression and in turn induced E-cadherin expression and reduced VEGF-A expression by suppressing activation of the AKT signaling pathway.
Conclusions
This study demonstrated that upregulated TM4SF1 and lost miR-141 expression were associated with advanced clinicopathological features and poor survival of pancreatic cancer patients. Lost miR-141 expression but induced TM4SF1 expression altered expression of VEGF-A and E-cadherin and promoted pancreatic cancer cell EMT and angiogenesis via the AKT signaling pathway, suggesting that targeting of miR-141 and TM4SF1 may be a potential therapeutic strategy to control pancreatic cancer.
Abbreviations
| TM4SF1: | = | Transmembrane-4-L-six-family-1 |
| EMT: | = | Epithelial-mesenchymal transition |
| qRT-PCR: | = | Quantitative real time polymerase chain reaction |
| VEGF-A: | = | Vascular endothelial growth factor-A |
| HUVECs: | = | Human umbilical vein endothelial cells |
| DMEM: | = | Dulbecco’s Modified Eagle’s Medium |
| FBS: | = | Fetal bovine serum |
| DMSO: | = | Dimethyl sulfoxide |
| CM: | = | Conditioned media |
| IACUC: | = | Institutional Animal Care and Use Committee |
Disclosure of Potential Conflicts of Interest
The authors declare that they have no competing interests in this study.
Authors’ Contributions
DX and FY were responsible for in vitro and in vivo experiments, respectively. KW, KZ and XX conducted chip data mining and data statistics, respectively. YA, XL and XHZ performed clinical sample testing and immunohistochemistry. JX, FX, XJY and LJX collected the clinical samples.
Contents
Upregulated TM4SF1 and lost miR-141 expression were associated with advanced clinicopathological features and poor survival of pancreatic cancer patients. Lost miR-141 expression but induced TM4SF1 expression promote pancreatic cancer cell EMT and angiogenesis via the AKT signaling pathway.
Availability of Data and Material
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Ethics Approval and Consent to Participate
This study was approved by the Ethics Committee of Gaochun People’s Hospital. All participants provided written informed consent form before enrollment into this study.
Supplementary material
Supplemental data for this article can be accessed on the publisher’s website.
Correction Statement
This article has been republished with minor changes. These changes do not impact the academic content of the article.