Long Non-coding RNA UCA1a Promotes Proliferation via PKM2 in Cervical Cancer

Cervical cancer is a common malignancy that affects women worldwide. The long non-coding RNA (lncRNA) urothelial cancer-associated 1a (UCA1a) is reported to be significantly upregulated in cervical cancer. However, the exact role of UCA1a in cervical cancer remains unknown. This study aimed to identify two core promoter regions in UCA1a, which are essential for CEBPA-dependent transcription and FOXL1-, FOXL4-, and FOXL6-dependent activation, respectively. RNA sequencing results showed that overexpression of UCA1a resulted in extensive changes in the gene expression profile of HeLa cells, especially in the signaling pathway that regulates tumorgenesis. Mass spectrometry assay was conducted to show that pyruvate kinase M2 (PKM2) was a UCA1a-interacting protein. The 400 ~ 800 nt long region of UCA1a at the 5' end and the A1B domain of PKM2 were critical for the UCA1a-PKM2 interaction. Functional assays were performed to show that PKM2 was sufficient and necessary for UCA1a-induced proliferation of HeLa cells, which was partly due to the regulating of nuclear translocation and stabilization of PKM2. These findings provide a novel mechanism for UCA1a to regulate Hela cells by ubiquitination degradation of PKM2 and suggest that UCA1a may play a key role in the progression of cervical cancer.