Long noncoding RNA DANCR promotes nasopharyngeal carcinoma progression by interacting with STAT3, enhancing IL-6/JAK1/STAT3 signaling

摘要

Nasopharyngeal carcinoma (NPC) is the most common type of malignancy of the neck and head in Southeast Asia and North Africa. Long noncoding RNA (LncRNA) Differentiation antagonizing nonprotein coding RNA (DANCR) has been reported to exert oncogenic functions in various malignant tumors. However, whether DANCR is involved in NPC tumorgenesis and its underlying mechanisms are still unknown. In the current study, we investigated the expression and biological functions of DANCR in NPC cells and found that DANCR is highly expressed in NPC cells and IL-6 stimulation upregulates DANCR expression through an STAT3-dependent manner. Besides, DANCR knockdown attenuates IL-6-induced proliferation and invasion of NPC cells. Furthermore, DANCR specifically interacts with STAT3 to promote STAT3 activation in NPC cells. Moreover, DANCR knockdown evidently decreases IL-6 induced the association between STAT3 and JAK1 in NPC cells. In addition, we also found that DANCR also indirectly binds to JAK1 through interacting with STAT3 under IL-6 stimulation in NPC cells. Taken together, the present study for the first time demonstrates that DANCR, acting as an oncogene in NPC, promotes NPC progression by interacting with STAT3 and enhancing JAK1 binding to STAT3 to strengthen IL-6/JAK1/STAT3 signaling, suggesting that it may be a potential target to be used as a novel strategy to develop NPC therapeutics.