Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 236, Issue 1, Pages 536-548Publisher
WILEY
DOI: 10.1002/jcp.29881
Keywords
gastric cancer; long non-coding RNA PVT1; metastasis; miR-30a; Snail
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Funding
- National Natural Science Foundation of China [31970877]
- Chongqing Natural Science Foundation Surface Project [cstc2019jcyj-msxmX0496]
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This study revealed that high expression of PVT1 is associated with poor prognosis in GC patients and can promote EMT process and metastasis of GC cells. PVT1 binds with miR-30a to increase Snail expression, affecting the migration of GC cells.
Although the incidence and mortality of gastric cancer (GC) are slowly decreasing, the overall prognosis of GC patients with distal metastasis remains dismal. Long non-coding RNA PVT1 has been verified to function as a tumor promoter in several types of cancer. However, the role of PVT1 in GC metastasis remains obscure. Herein, we found that PVT1 was highly expressed in GC tissues and high PVT1 level was associated with tumor stage, lymph node metastasis, and poor prognosis. Overexpression of PVT1 significantly elevated epithelial-to-mesenchymal transition (EMT) marker (N-cadherin, ZEB1, and ZEB2) levels and promoted GC cell EMT process and tumor metastasis in vitro and in vivo. Mechanistically, Snail was identified as a direct target of miR-30a. PVT1 could bind with miR-30a and increase the expression of Snail by acting as a competing endogenous RNA, whereas re-expression of miR-30a in GC cells rescued the EMT markers, decreased Snail level, and inhibited GC cell migration. Taken together, these findings provide a new light on PVT1 in the pathogenesis and development of GC and an important implication for future therapy of the GC.
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