Long Non-Coding RNA GATA3-AS1 Promotes 5-Fluorouracil Resistance of Ovarian Cancer via Mediating miR-6771-3p/SOX4 Target Axis

Abstract

Ovarian cancer (OC) ranks as the 5th highest cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) exert significant effects on chemotherapy resistance. The effects of lncRNA GATA3-AS1 on the 5-Fluorouracil (5-FU) resistance in ovarian carcinoma were explored in the current study. The results showed that GATA3-AS1 was highly expressed in OC tissues and 5-FU resistant OC cells. Moreover, GATA3-AS1 knockdown reduced 50% inhibitory concentration (IC50) of 5-Fluorouracil and promoted cell apoptosis, while GATA3-AS1-overexpression showed the opposite effect. In vivo experiment and murine xenograft assay indicated GATA3-AS1 knockdown inhibited neoplasm growth, promoted cell apoptosis, and altered the expression level of apoptosis-associated proteins. GATA3-AS1 promoted SOX4 expression, a well-known transcription factor regulating apoptosis, via targeting miR-6771-3p. In summary, our findings suggested GATA3-AS1 was associated with OC 5-Fluorouracil viaregulating miR-6771-3p/SOX4, providing novel insights into OC chemoresistance.