Evidence has shown the importance of long non-coding RNAs (lncRNAs) during angiogenesis and lung cancer progression. However, the potential functions of TNK2-AS1 in non-small cell lung cancer (NSCLC) remain elusive. By lncRNA profiling, we identified TNK2-AS1 as a novel oncogenic lncRNA in NSCLC. TNK2-AS1 was significantly upregulated in NSCLC and correlated with poor prognosis. We found that TNK2-AS1 could increase viability and migration of NSCLC cells in vitro. TNK2-AS1 also promoted NSCLC xenograft tumor growth and metastasis in vivo. TNK2-AS1 could interact with STAT3 to increase its protein stability by protecting it from proteasome-mediated degradation. STAT3 could also bind TNK2-AS1 promoter to trigger its transcription. The positive feedback loop between STAT3 and TNK2-AS1 therefore augmented STAT3 signaling by elevating VEGFA expression to facilitate angiogenesis. Collectively, our work has elucidated a novel mechanism of TNK2-AS1-mediated angiogenesis by enforcing STAT3/VEGFA signaling and may provide a potential target for therapeutic intervention.
Keywords: NSCLC; STAT3; TNK2-AS1; VEGFA.
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