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 overexpression inhibited cell viability and promoted cell apoptosis upon DDP treatment through the Bcl-2/caspase-3 apoptotic signaling. It was hypothesized that PTEN mRNA expression 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 apoptotic 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.