Long non­coding RNA HAND2­AS1/miR­106a/PTEN axis re­sensitizes cisplatin­resistant 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 non­coding RNA (lncRNA)­microRNA (miRNA)­mRNA axis participating in ovarian cancer DDP­resistance based on the critical roles of non­coding RNAs, including lncRNAs and miRNAs, in carcinogenesis. According to online data and experimental results, lncRNA HAND2­AS1 expression was significantly downregulated within ovarian carcinoma, especially within recurrent and DDP­resistant ovarian carcinoma. The expression of HAND2­AS1 was also shown to be markedly inhibited in SKOV3/DDP (DDP) cells with resistance to DDP. In SKOV3/DDP cells, HAND2­AS1 overexpression inhibited cell viability and promoted cell apoptosis upon DDP treatment through the Bcl­2/caspase­3 apoptotic signaling. It was hypothesized that PTEN mRNA expression was also markedly inhibited in SKOV3/DDP ovarian cancer cells, while HAND2­AS1 overexpression rescued PTEN proteins and blocked PI3K/AKT signaling activation. Moreover, miR­106a was found to bind directly to PTEN 3' UTR and HAND2­AS1. Upon DDP treatment, miR­106a overexpression in SKOV3/DDP cells promoted cell viability. It inhibited cell apoptosis through the Bcl­2/caspase­3 apoptotic signaling pathway and downregulated the protein levels of PTEN and upregulated PI3K/AKT signaling activity. Furthermore, miR­106a overexpression partially reversed the effect of HAND2­AS1 overexpression upon PTEN proteins and SKOV3/DDP cell proliferation upon DDP treatment. In conclusion, a lncRNA HAND2­AS1/miR­106a/PTEN axis that re­sensitizes DDP­resistant SKOV3/DDP cells to DDP treatment has been established.