Long non‑coding RNA HAND2‑AS1/miR‑106a/PTEN axis re‑sensitizes cisplatin‑resistant ovarian cells to cisplatin treatment

Abstract

Cisplatin (DDP) resistance in patients suffering from ovarian cancer is a considerable hurdle to successful treatment. The present study aimed to identify a possible long non‑coding RNA (lncRNA)‑microRNA (miRNA)‑mRNA axis participating in ovarian cancer DDP‑resistance based on the critical roles of non‑coding RNAs, including lncRNAs and miRNAs, in carcinogenesis. According to online data and experimental results, lncRNA HAND2‑AS1 expression was significantly downregulated within ovarian carcinoma, especially within recurrent and DDP‑resistant ovarian carcinoma. The expression of HAND2‑AS1 was also shown to be markedly inhibited in SKOV3/DDP (DDP) cells with resistance to DDP. In SKOV3/DDP cells, HAND2‑AS1 over‑ expression inhibited cell viability and promoted cell apoptosis upon DDP treatment through the Bcl‑2/caspase‑3 apoptotic signaling. It was hypothesized that PTEN mRNA expres‑ sion was also markedly inhibited in SKOV3/DDP ovarian cancer cells, while HAND2‑AS1 overexpression rescued PTEN proteins and blocked PI3K/AKT signaling activation. Moreover, miR‑106a was found to bind directly to PTEN 3' UTR and HAND2‑AS1. Upon DDP treatment, miR‑106a overexpression in SKOV3/DDP cells promoted cell viability. It inhibited cell apoptosis through the Bcl‑2/caspase‑3 apop‑ totic signaling pathway and downregulated the protein levels of PTEN and upregulated PI3K/AKT signaling activity. Furthermore, miR‑106a overexpression partially reversed the effect of HAND2‑AS1 overexpression upon PTEN proteins and SKOV3/DDP cell proliferation upon DDP treatment. In conclusion, a lncRNA HAND2‑AS1/miR‑106a/PTEN axis that re‑sensitizes DDP‑resistant SKOV3/DDP cells to DDP treatment has been established.