METTL3‐mediated m6A modification of lnc RNA RHPN1‐AS1 enhances cisplatin resistance in ovarian cancer by activating PI3K/AKT pathway

BACKGROUND: Cisplatin resistance is a big challenge for ovarian cancer (OC) therapy. The abnormal expression of long noncoding RNAs (lncRNAs) regulated by N6‐methyladenosine (m6A) modification has been confirmed to play the crucial roles in OC. The aim of this study is to explore the regulatory mechanism of lncRNA RHPN1‐AS1 on OC with cisplatin resistance. METHODS: The real‐time reverse transcription‐polymerase chain reaction was carried out to confirm the expression of RHPN1‐AS1 and methyltransferase‐like 3 (METTL3) in OC. The effects of RHPN1‐AS1 on cisplatin‐resistant OC cells were identified by cell functional experiments and animal experiment. Western blotting was performed to detect the effect of RHPN1‐AS1 on PI3K/AKT pathway. Moreover, methylated RNA immunoprecipitation and RNA stability assays confirmed the interaction between RHPN1‐AS1 and METTL3. RESULTS: RHPN1‐AS1 and METTL3 were confirmed to be overexpressed in OC. After transfecting RHPN1‐AS1 overexpression or RHPN1‐AS1 knockdown vectors into cisplatin‐resistant OC cells, it was found that upregulating RHPN1‐AS1 contributed to cell viability, migration, invasion, and tumor growth in vivo. In addition, RHPN1‐AS1 could enhance the protein levels of PI3K and phosphorylated AKT in cisplatin‐resistant OC cells, and METTL3 could enhance the stability of RHPN1‐AS1 by the m6A modification. CONCLUSION: Overall, this study revealed that METTL3‐mediated m6A modification of RHPN1‐AS1 accelerates cisplatin resistance in OC by activating PI3K/AKT pathway.