A novel positive feedback regulation between long noncoding RNA UICC and IL-6/STAT3 signaling promotes cervical cancer progression

Long noncoding RNAs (lncRNAs), a novel class of transcripts that have critical roles in carcinogenesis and progression, have emerged as important gene expression modulators. However, the pathophysiological contributions and the underlying mechanisms of specific lncRNAs in cervical cancer remain largely unknown. Here, using transcriptome microarray analysis, we identified a novel lncRNA termed lncRNA upregulated in cervical cancer (lnc-UICC) that was highly expressed in cervical cancer tissue.lnc-UICC expression in cervical cancer was associated with FIGO stage, lymph node metastasis and prognosis. Through gain- and loss-of-lnc-UICC expression, we found lnc-UICC could significantly promote tumor growth and metastasis in vitro and in vivo. Mechanistically, lnc-UICC promoted STAT3 activation through two complementary ways. lnc-UICC could regulate the IL-6 transcription through binging to IL-6 promoter. lnc-UICC also directly interacted with the phospho-STAT3, and increased its protein stability by protecting it from proteasome-dependent degradation. Moreover, we revealed that lnc-UICC was a STAT3-responsive lncRNA, as STAT3 could bind to the lnc-UICC promoter to enhance its transcription, suggesting that there exists a positive feedback loop between lnc-UICC and IL-6/STAT3 signaling. In sum, therefore, we have identified an lncRNA-based IL-6/STAT3 signaling regulatory circuit that promotes tumorigenesis and metastasis in cervical cancer cells, highlighting the role that lnc-RNAs can play in tumor progression.