Abstract

Ovarian carcinoma (OC) is a fatal malignant tumor that seriously threatens the health and survival of women. Olaparib is a highly promising drug for OC treatment of ovarian cancer. Long non-coding RNA (lncRNA) THUMPD3-AS1, which is related to autophagy, has been proven to be carcinogenic in OC. However, the effects and mechanisms of THUMPD3-AS1 combined with Olaparib on ovarian cancer remain unclear. Upregulation of THUMPD3-AS1 was observed in OC tissues and cells. Loss-of-function assays unraveled that silencing THUMPD3-AS1 contributed to autophagy and promoted cell apoptosis and DNA damage in OC cells. Besides, our findings validated that olaparib exerted a stimulative role in autophagy, cell apoptosis and DNA damage. Of note, knockdown of THUMPD3-AS1 intensified the effects of olaparib on OC cells. Subsequently, we certified that THUMPD3-AS1 depletion enlarged the suppression of PI3K/AKT/mTOR pathway caused by olaparib. The function of THUMPD3-AS1 in olaparib-treated OC cells was achieved by regulating PI3K/AKT/mTOR signaling. Animal experiment further confirmed that downregulating THUMPD3-AS1 enhanced olaparib sensitivity to hinder the in vivo growth of OC cells through inhibiting PI3K/AKT/mTOR pathway. Our research revealed THUMPD3-AS1 as a promising target for OC therapy.