shRNA-mediated silencing of TARBP2 inhibits NCI-H1299 non-small cell lung cancer cell invasion and migration via the JNK/STAT3/AKT pathway
Metastasis is a major cause of lung cancer-associated mortality. The current study aimed to investigate the effects and mechanisms of TAR (human immunodeficiency virus 1) RNA binding protein 2 (TARBP2) in the invasion and migration of non-small cell lung cancer in vitro. The highly metastatic cell c...
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Veröffentlicht in: | Molecular medicine reports 2016-10, Vol.14 (4), p.3725-3730 |
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Zusammenfassung: | Metastasis is a major cause of lung cancer-associated mortality. The current study aimed to investigate the effects and mechanisms of TAR (human immunodeficiency virus 1) RNA binding protein 2 (TARBP2) in the invasion and migration of non-small cell lung cancer in vitro. The highly metastatic cell clone H1299/M02 was obtained by TARBP2 overexpression. Expression of TARBP2 in H1299/M02 was also downregulated to different levels via small hairpin RNAs (shRNAs). Subsequent to TARBP2 silencing, the proliferation of H1299/M02 cells was predominantly unaffected, while invasion and migration were significantly inhibited. A positive correlation was observed between invasion and migration and the level of TARBP2 silencing in vitro. Western blotting and reverse transcription-quantitative polymerase chain reaction indicated that the protein expression levels of amyloid β (A4) precursor protein (APP) and zinc finger protein 395 (ZNF395) were upregulated, while expression levels of pro-metastatic proteins including interleukin (IL)-1β, IL-8, cyclooxygenase (COX)-2, matrix metalloproteinase 2 (MMP2) and MMP9 were downregulated. Phosphorylation of c-Jun N-terminal kinase (JNK), signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) were also inhibited. Overexpression of TARBP2 was suggested to be involved in the metastasis of H1299/M02 cells. Silencing of TARBP2 was able to upregulate levels of APP and ZNF395, in addition to inhibiting metastasis-promoting cytokines, the JNK/STAT3/AKT pathway and COX-2 to attenuate the invasion and migration of cancer cells. |
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ISSN: | 1791-2997 1791-3004 |
DOI: | 10.3892/mmr.2016.5723 |