4.5 Article

LncRNA TP73-AS1 enhances the malignant properties of pancreatic ductal adenocarcinoma by increasing MMP14 expression through miRNA-200a sponging

Journal

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 25, Issue 7, Pages 3654-3664

Publisher

WILEY
DOI: 10.1111/jcmm.16425

Keywords

ceRNA; miR‐ 200a; mmp14; pancreatic ductal adenocarcinoma; TP73‐ AS1

Funding

  1. Jiangsu Provincial Commission of Health and Family Planning [LGY2018080]
  2. Nantong Municipal Commission of Health and Family Planning [QA2020040]
  3. National Natural Science Foundation of China [81672903]
  4. Nantong Science and Technology Bureau [GJZ17096, JC2019141]

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This study identified TP73-AS1 as a novel host factor overexpressed in PDAC tissues, correlating with poor prognosis for PDAC patients and indicating its potential as a therapeutic target for anti-PDAC treatment.
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.

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