Pseudogene AKR1B10P1 enhances tumorigenicity and regulates epithelial-mesenchymal transition in hepatocellular carcinoma via stabilizing SOX4.

Pseudogenes exert potential functions in tumorigenicity and tumour process in human beings. In our previous research on oncogene AKR1B10 in hepatocellular carcinoma (HCC), its pseudogene, AKR1B10P1, was preliminarily noticed being anomalistic transcribed, whereas whether AKR1B10P1 plays any specific function in HCC is poorly understood. By using shRNA transfection and lentiviral infection, we regulated the expression of ARK1B10P1 transcript and the relative targets in two ways. As we discovered, pathological transcription of AKR1B10P1 in HCC cells significantly promotes cell growth and motility either in vitro or in vivo. AKR1B10P1 was correlated with relatively dismal features of HCC. The epithelial-mesenchymal transition (EMT) was enhanced by up-regulating AKR1B10P1. And, a potential sequence of AKR1B10P1 transcript was discovered directly interacting with miR-138. SOX4, a pivotal promotor of EMT, was validated as the down-streaming target of miR-138. Mechanistically, degradation of SOX4 mRNA induced by miR-138 was effectively abrogated by AKR1B10P1. In conclusion, pseudogene AKR1B10P1 exerts stabilizing effect on SOX4 in HCC, associated EMT process, by directly sponging miR-138, which post-transcriptionally modulates SOX4's regulating gene.