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  • Title: METTL3-mediated m6A modification of lnc RNA RHPN1-AS1 enhances cisplatin resistance in ovarian cancer by activating PI3K/AKT pathway.
    Author: Cui S.
    Journal: J Clin Lab Anal; 2022 Dec; 36(12):e24761. PubMed ID: 36336887.
    Abstract:
    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.
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