HOXD-AS1 Exerts Oncogenic Functions and Promotes Chemoresistance in Cisplatin-Resistant Cervical Cancer Cells.

Abstract

Long noncoding RNAs (lncRNAs) are important regulators in various human diseases. The lncRNA HOXD-AS1 is a tumor promoter in ovarian cancer, glioma, and lung cancer, but the specific effects of HOXD-AS1 on cervical cancer (CC) chemoresistance remain unclear. Here, the level of HOXD-AS1 in nonmalignant and CC tissues as well as in CC cells and cisplatin-resistant CC cells was determined. qRT-PCR indicated that HOXD-AS1 was overexpressed in CC tissues and cisplatin-resistant CC cells. Loss-of-function assays showed that downregulation of HOXD-AS1 expression suppressed chemoresistance of cisplatin-resistant CC cells. HOXD-AS1 targeted miR-130a-3p, and in gain-of-function assays miR-130a-3p could reverse cisplatin resistance of CC cells. miR-130a-3p in turn targeted zinc finger E-box homeobox 1 (ZEB1). These results collectively show that HOXD-AS1 can act as a competing endogenous RNA to upregulate ZEB1 expression via miR-130a-3p. The effects of the HOXD-AS1-miR-130a-3p-ZEB1 axis on cisplatin resistance of cisplatin-resistant CC cells were supported by rescue assay results. In summary, HOXD-AS1 enhanced chemoresistance of cisplatin-resistant CC cells by modulating miR-130a-3p/ZEB1 axis expression.