Through this feedback loop, STAT3 activated the transcription of target gene IL6, which was the initiator of IL6/JAK2/STAT3 and subsequently activated the STAT3 activity by JAK2 to amplify the effects of signaling.[23b] In our study, the enhancement of IL‐6 and p‐JAK2 expression were detected in C21orf58‐overexpressed HCC cells accompanied by increase of p‐STAT3, which might be the results caused by forward feedback loop of STAT3, amplifying STAT3 signaling and endowing HCC with malignancies. This evidence concerns the gene IL6 and hepatocellular carcinoma.