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Linc-pint inhibits early stage pancreatic ductal adenocarcinoma growth through TGF-β pathway activation
Huimin Lu1, Dujiang Yang1, Ling Zhang1
1Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Abstract:
Long intergenic non-protein coding RNA, p53 induced transcript (Linc-pint) is a newly identified long non-coding RNA, which has demonstrated antitumor activities in various types of cancer. The present study aimed to investigate the role of Linc-pint in pancreatic ductal adenocarcinoma (PDAC). Plasma samples from patients with PDAC, and PDAC and normal cell lines were used in the study. Gene expression was analyzed by reverse transcription-quantitative polymerase chain reaction. Western blotting was used to assess protein level. Transforming growth factor β1 (TGF-β1) plasma level was determined by ELISA. Cancer cell proliferation was measured in vitro with the Cell Counting Kit-8 assy. The results demonstrated that Linc-pint plasma levels were significantly lower in patients with stage 0-1 PDAC compared with healthy controls. In addition, Linc-pint downregulation effectively distinguished patients with PDAC from healthy controls. Linc-pint and TGF-β1 plasma levels were positively correlated in patients with PDAC but not in healthy controls. Furthermore, Linc-pint overexpression upregulated TGF-β1 expression in PDAC cells but not in normal pancreatic ductal cells; however, exogenous TGF-β1 exhibited no significant effects on Linc-pint expression. Linc-pint overexpression and TGF-β1 both inhibited PDAC cell proliferation, whereas treatment with a TGF-β inhibitor reduced their inhibitory effects on cell proliferation. In conclusion, results from the present study suggested that Linc-pint may inhibit early stage PDAC growth through TGF-β pathway activation.
Insights
Long intergenic non-protein coding RNA (Linc-pint) shows potential as a biomarker for early pancreatic ductal adenocarcinoma (PDAC). Lower Linc-pint levels in patients suggest a role in PDAC development via TGF-β pathway activation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Long intergenic non-protein coding RNA (Linc-pint) exhibits antitumor properties in various cancers.
- The specific role of Linc-pint in pancreatic ductal adenocarcinoma (PDAC) requires further investigation.
Purpose of the Study:
- To investigate the role and clinical significance of Linc-pint in pancreatic ductal adenocarcinoma (PDAC).
- To explore the relationship between Linc-pint, TGF-β1, and PDAC cell proliferation.
Main Methods:
- Analysis of Linc-pint and TGF-β1 plasma levels using RT-qPCR, Western blotting, and ELISA.
- Assessment of PDAC cell proliferation in vitro.
- Investigation of gene expression changes in response to Linc-pint and TGF-β1 manipulation.
Main Results:
- Significantly lower Linc-pint plasma levels were observed in early-stage PDAC patients compared to healthy controls.
- Linc-pint plasma levels positively correlated with TGF-β1 levels in PDAC patients.
- Linc-pint overexpression upregulated TGF-β1 and inhibited PDAC cell proliferation, an effect partially reversed by TGF-β inhibition.
Conclusions:
- Linc-pint may serve as a potential diagnostic biomarker for early-stage PDAC.
- Linc-pint likely inhibits early PDAC growth by activating the TGF-β signaling pathway.
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