The novel long noncoding RNA AU021063, induced by IL-6/Arid5a signaling, exacerbates breast cancer invasion and metastasis by stabilizing Trib3 and activating the Mek/Erk pathway.
Cancer Lett
; 520: 295-306, 2021 11 01.
Article
in En
| MEDLINE
| ID: mdl-34389433
ABSTRACT
Interleukin (IL-6) is a pleotropic cytokine with both tumor-promoting and -inhibitory effects on breast cancer growth. However, the mechanisms governing the outcome of IL-6 on cancer progression remain to be clarified. Our study unraveled a novel long noncoding RNA (lncRNA) AU021063 downstream of IL-6 signaling. We found that IL-6 induced the expression of AU021063 predominantly in breast cancer compared to other cancer types. Mechanistically, IL-6 induced AT-rich interactive domain 5a (Arid5a) expression, which promotes the transcription of AU021063. In turn, AU021063 promotes breast cancer metastasis through stabilizing tribbles homolog 3 (Trib3) and activating Mek/Erk signaling pathway. Genetic ablation of either Arid5a, AU021063 or Trib3 abolished breast cancer metastasis in vitro and in vivo. Overall, our study highlights the importance of IL-6-Arid5a-AU021063 axis in regulating breast cancer invasiveness and metastasis, which may provide potential novel therapeutics for breast cancer.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Breast Neoplasms
/
Interleukin-6
/
Cell Cycle Proteins
/
DNA-Binding Proteins
/
RNA, Long Noncoding
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cancer Lett
Year:
2021
Document type:
Article