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LncRNA TP73-AS1 enhances the malignant properties of pancreatic ductal adenocarcinoma by increasing MMP14 expression through miRNA -200a sponging
Authors:Haiyan Miao  Jingjing Lu  Yibing Guo  Hongquan Qiu  Yu Zhang  Xihao Yao  Xiaohong Li  Yuhua Lu
Affiliation:1. Research Center of Clinical Medical and Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China;2. Research Center of Clinical Medical and Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China

Contribution: Data curation (equal), Methodology (equal), Project administration (equal), Resources (equal), Software (equal);3. Research Center of Clinical Medical and Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China

Contribution: Methodology (equal), Resources (equal), Software (equal);4. Research Center of Clinical Medical and Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China

Contribution: Data curation (equal), Methodology (equal), Supervision (equal), Writing - original draft (equal);5. Research Center of Clinical Medical and Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China

Contribution: Methodology (equal), Software (equal), Writing - original draft (equal), Writing - review & editing (equal);6. Research Center of Clinical Medical and Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China

Contribution: Data curation (equal), Writing - original draft (equal)

Abstract:Pancreatic ductal adenocarcinoma (PDAC) is an invasive and aggressive cancer that remains a major threat to human health across the globe. Despite advances in cancer treatments and diagnosis, the prognosis of PDAC patients remains poor. New and more effective PDAC therapies are therefore urgently required. In this study, we identified a novel host factor, namely the LncRNA TP73-AS1, as overexpressed in PDAC tissues compared to adjacent healthy tissue samples. The overexpression of TP-73-AS1 was found to correlate with both PDAC stage and lymph node metastasis. To reveal its role in PDCA, we targeted TP73-AS1 using LnRNA inhibitors in a range of pancreatic cancer (PC) cell lines. We found that the inhibition of TP73-AS1 led to a loss of MMP14 expression in PC cells and significantly inhibited their migratory and invasive capacity. No effects of TP73-AS1 on cell survival or proliferation were observed. Mechanistically, we found that TP73-AS1 suppressed the expression of the known oncogenic miR-200a. Taken together, these data highlight the prognostic potential of TP73-AS1 for PC patients and highlight it as a potential anti-PDAC therapeutic target.
Keywords:ceRNA  miR-200a  mmp14  pancreatic ductal adenocarcinoma  TP73-AS1
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