Open AccessLNRRIL 6, a novel long noncoding RNA , protects colorectal cancer cells by activating the IL ‐6– STAT 3 pathway
Author(s) -
Wang Jiaxing,
Zhou Junfeng,
Jiang Caiyun,
Zheng Jing,
Namba Hiroki,
Chi Pan,
Asakawa Tetsuya
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12538
Subject(s) - autocrine signalling , long non coding rna , stat3 , cancer research , colorectal cancer , biology , cell growth , signal transduction , downregulation and upregulation , cancer , cell culture , microbiology and biotechnology , gene , genetics
Long noncoding RNA s (lnc RNA s) are emerging as critical regulators of cancer. There is a comparable number of lnc RNA s to protein‐coding genes, but the expression patterns, functions, and molecular mechanisms of most lnc RNA s in colorectal cancer ( CRC ) remain unclear. In this study, we report the identification of a novel lnc RNA , named long noncoding RNA regulating IL ‐6 transcription ( LNRRIL 6), which is upregulated in CRC tissues and cell lines. Increased LNRRIL 6 expression is associated with aggressive clinicopathological characteristics and poor prognosis of CRC patients. Functional experiments showed that enhanced expression of LNRRIL 6 promotes CRC cell proliferation and survival in vitro and CRC tumor growth in vivo . Conversely, depletion of LNRRIL 6 inhibits CRC cell proliferation and survival in vitro and CRC tumor growth in vivo . Mechanistically, we revealed that LNRRIL 6 physically binds to the IL ‐6 promoter, thereby increasing IL ‐6 transcription, inducing IL ‐6 autocrine signaling, and activating the IL ‐6/ STAT 3 pathway. The expression of IL ‐6 is positively associated with that of LNRRIL 6 in CRC tissues. Blocking the IL ‐6/ STAT 3 pathway using the FDA ‐approved IL ‐6‐receptor antagonist antibody, tocilizumab, abolished the oncogenic role of LNRRIL 6 in CRC . Taken together, these findings identify a novel lnc RNA , LNRRIL 6, that promotes CRC cell survival through activation of the IL ‐6/ STAT 3 pathway and suggest that LNRRIL 6 may be a potential prognostic biomarker and therapeutic target for CRC .