SP1-induced lncRNA MCF2L-AS1 promotes cisplatin resistance in ovarian cancer by regulating IGF2BP1/IGF2/MEK/ERK axis

다국어 초록 (Multilingual Abstract)

Objective: Cisplatin resistance is a huge problem encountered in ovarian cancer treatment. Our study probed the roles and the underlying mechanisms of lncRNA MCF2L-AS1 in ovarian cancer cisplatin-resistance.
Methods: SKOV3 and IGROV-1 cells were subjected to gradually increasing concentrations of cisplatin to construct ovarian cancer cisplatin-resistance cells. Cell proliferation was evaluated by cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and PI staining. The relationships between SP1, MCF2L-AS1 and insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) were verified by RNA pull-down, RIP, ChIP and dual- luciferase reporter gene assay, respectively. Tumor xenograft experiment was employed to evaluate the effects of MCF2L-AS1 silencing on ovarian cancer cisplatin-resistance in vivo. TUNEL staining and immunohistochemistry were performed in tumor tissue.
Results: MCF2L-AS1 and IGF2BP1 were upregulated in cisplatin-resistant cells. MCF2L-AS1 silencing suppressed cell proliferation of cisplatin-resistant cells, while promoted the apoptosis, suggesting that MCF2L-AS1 knockdown suppressed ovarian cancer cells cisplatin-resistance. Meanwhile, MCF2L-AS1 silencing enhanced cisplatin sensitivity in ovarian cancer parental cells and IGF2BP1 overexpression impaired cisplatin sensitivity of parental cells. MCF2L-AS1 activated IGF2/ MEK/ERK pathway through interacting with IGF2BP1. Transcription factor SP1 activated MCF2L- AS1 expression. MCF2L-AS1 knockdown inhibited ovarian cancer cisplatin-resistance in vivo. Conclusion: SP1-induced MCF2L-AS1 promoted ovarian cancer cisplatin-resistance through activation of IGF2/MEK/ERK pathway via interacting with IGF2BP1.

참고문헌 (Reference)

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