Colorectal cancer (CRC) is one of the most common malignant tumors and one of the leading causes of cancer-related death in both men and women. The prognosis of CRC remains poor due to the advanced stage and cancer metastasis at the time of diagnosis. However, the exact mechanism of tumorigenesis in CRC remains unclear. Long non-coding RNAs (lncRNAs), which refer to transcripts longer than 200 nucleotides that are not translated into protein, are known to play important roles in multiple human cancers. Lnc-DILC is reported to be an important tumor suppressor gene and its inactivation is closely associated with liver cancer stem cells. However, the role of lnc-DILC in CRC remains to be elucidated. In the present study, we observed that lnc-DILC overexpression inhibited the growth and metastasis of CRC cells. Consistently, lnc-DILC knockdown facilitated the proliferation and metastasis of CRC cells. Mechanically, lnc-DILC suppressed CRC cell progression via IL-6/STAT3 signaling inactivation. More importantly, the specific STAT3 inhibitor S3I-201 and IL-6R inhibitor tocilizumab abolished the discrepancy of growth and metastasis capacity between lnc-DILC-interference CRC cells and control cells, which further confirmed that IL-6/STAT3 signaling was required in lnc-DILC-disrupted CRC cell growth and metastasis. Taken together, our results suggest that lnc-DILC is a novel CRC suppressor and may prove to be an inhibitor of CRC progression by inactivating IL-6/STAT3 signaling.
Keywords: Colorectal cancer; Metastasis; Proliferation; STAT3; lnc-DILC.
Copyright © 2018. Published by Elsevier B.V.