The lncKLF6/KLF6 feedback loop regulates the growth of non-small cell lung cancer.

Non-small lung cancer (NSCLC) is one of the most common causes of cancer-associated death worldwide. Long noncoding RNAs (lncRNAs) regulate cancer initiation and progression through different mechanisms. In the present study, we characterized a novel lncRNA named lncKLF6, which was upregulated in NSCLC and associated with poor clinical outcomes. lncKLF6 inhibited Kruppel-like factor 6 (KLF6) transcription and then facilitated NSCLC growth. lncKLF6 is associated with the epigenetic repressor BMI1 and regulates its stability via recruiting deubiquitinase USP22. Moreover, it was revealed that lncKLF6 was a KLF6-responsive lncRNA, as KLF6 could occupy the lncKLF6 promoter to facilitate its transcription. The negative feedback loop of lncKLF6 and KLF6 continuously enhanced the oncogenic effects. Thus, our study elucidates the mechanism of lncKLF6-mediated growth via suppression of KLF6, which provides the promising target for developing new therapeutic strategy in NSCLC.