Biochemical and Biophysical Research Communications, Vol.526, No.4, 857-864, 2020
LncRNA TLR8-AS1 promotes metastasis and chemoresistance of ovarian cancer through enhancing TLR8 mRNA stability
Ovarian cancer is diagnosed as the most deadly gynecological tumor. Ovarian cancer metastasis affects chemoresistance and confers poor patient prognosis. In present work, we intended to elucidate whether long non-coding RNAs (lncRNAs) TLR8-AS1 regulated cell metastasis and chemoresistance of ovarian cancer, and uncover the molecular mechanism of TLR8-AS1 in the modulation of ovarian cancer progression. Firstly, bioinformatics analyses identified TLR8-AS1 as a cancer-associated fibroblasts regulated lncRNA in ovarian cancer. Further experiments revealed that TLR8-AS1 augmented cell metastasis and chemoresistance of ovarian cancer in vitro and in vivo. Moreover, TLR8-AS1 upregulates TLR8 by stabilizing TLR8 mRNA, thus activating NF-kappa B signaling and promoting ovarian cancer metastasis and chemoresistance. Besides, TCGA data analysis suggested that TLR8-AS1 is elevated in ovarian cancer in comparison to adjacent non-cancerous tissues. High TLR8-AS1 expression levels were measured in metastatic ovarian cancer and correlated with poor patient prognosis. The clinical data supported the mechanism and biological significance of TLR8-AS1 dysregulation in ovarian cancer development. Our work demonstrates that TLR8-AS1 can be applied as a diagnostic and prognostic indicator for ovarian cancer, and maybe an alternative target for the treatment of ovarian cancer. (C) 2020 Elsevier Inc. All rights reserved.