Journal
BIOENGINEERED
Volume 13, Issue 1, Pages 1602-1611Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/21655979.2021.2020548
Keywords
Gastric cancer; invasion; PARP2; proliferation; miR-128; CCL2; migration
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Funding
- Shanghai Pudong New Area Science and Technology Development Fund [PKJ2017-Y25]
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This study revealed that lncRNA CCL2 regulates the proliferation, migration, and invasion of gastric cancer through the miR-128/PARP2 signaling pathway. These findings provide a potential new strategy for the treatment of gastric cancer.
Amounts of studies have revealed long non-coding RNA (lncRNA) was related to the development of gastric cancer. Here, our results suggested the function and regulatory mechanism of CCL2 in gastric cancer. Quantitative polymerase-chain reaction (qPCR) was employed to inspect lncRNA CCL2 and miR-128 expression in normal gastric cell line (GES-1) and tumor cell lines (HGC-27 and MKN-45). The effects of CCL2 and miR-128 were measured via Luciferase reporter test. Western blot was used to check PARP2 protein expression. CCL2 expression and PARP2 protein levels were up-regulated, while miR-128 expression was obviously lower. Meanwhile, CCL2 down-regulating significantly repressed the proliferation, migration, and invasion by regulating miR-128. In addition, we proved miR-128 was a direct target of CCL2 through double luciferase assay and bioinformatics analysis. Moreover, miR-128 markedly inhibited the proliferation, migration, and invasion in gastric cancer. More importantly, miR-128 could reverse the effects of lncRNA CCL2 knocked down. PARP2-si obviously suppressed in gastric cancer proliferation, migration, and invasion. Meanwhile, miR-128 mimic and the knockout of CCL2 distinctly decreased PARP2 protein level. Additionally, luciferase report experiments certificated that PARP2 targeted miR-128, implying PARP2 directly interacted with miR-128 in gastric cancer. More interestingly, the downregulation of PARP could reverse the trend triggered by miR-128 inhibitor in gastric tumor. All over these results showed lncRNA CCL2 played importance of role in gastric tumor via miR-128/PARP2 axis signal pathway. LncRNA CCL2 accelerated gastric cancer progression by regulating miR-128/PARP2 signaling pathway, providing a novel possible strategy for the treatment of gastric cancer.
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