Feedback Loop of DUXAP8/miR-214-3p/KLF13 Facilitates Hepatocellular Carcinoma Progression and Serves as an Indicator of Tumor Microenvironment via Impacting Piezo1.

Pseudogenes are barely transcribed normally, but some of them are transcribed as long non-coding RNAs during tumorigenesis. The pathological features of pseudogenes in hepatocellular carcinoma (HCC) have not been illustrated clearly. Here, we engaged the pseudogene DUXAP8 into a feedback loop affecting the HCC indicator Piezo1 and concerning the HCC tumor microenvironment (TME). As we discovered, the DUXAP8 transcript was detectable in HCC. The transcriptional activity of DUXAP8 in HCC is associated with dismal HCC clinicopathological features. By depleting DUXAP8, the HCC cells presented the inhibition of cell proliferation along with significant cell apoptosis in vitro and potently suppressed the HCC tumorigenesis ability in vivo. Combined with the ChIP assay, the direct interaction of either the DUXAP8 transcript/miR-214-3p or miR-214-3p/KLF13 mRNA was verified, and the promoting effect of KLF13 on DUXAP8 transcription was also validated, which further illustrates a positive feedback loop of DUXAP8/miR-214-3p/KLF13. Moreover, KLF13 was found to facilitate Piezo1 transcription. As concluded, our findings suggest that the pseudogene DUXAP8 promotes HCC tumorigenesis through the feedback loop of DUXAP8/miR-214-3p/KLF13 and participates in HCC TME modulation by impacting Piezo1.