OncoTargets and Therapy (Feb 2024)

METTL3/MALAT1/ELAVL1 Axis Promotes Tumor Growth in Ovarian Cancer

  • Xiong J,
  • Lian W,
  • Zhao R,
  • Gao K

Journal volume & issue
Vol. Volume 17
pp. 85 – 97

Abstract

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Jian Xiong,1,* Wenqin Lian,2,* Rui Zhao,1 Kefei Gao1 1Department of Obstetrics and Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kefei Gao; Rui Zhao, Department of Obstetrics and Gynaecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, Guangdong, 510623, People’s Republic of China, Email [email protected]; [email protected]: Studies increasingly recognize the role of N6-methyladenosine (m6A) modification in cancer occurrence and development. METTL3 is a core catalytic subunit of m6A-modified methyltransferases complex, but its regulatory mechanism in ovarian cancer (OC) is not clear.Methods: In this study, GEPIA 2.0 database was applied for expression analysis, survival analysis and correlation analysis for OC. Additionally, in vitro and in vivo assays were conducted to explore regulatory mechanisms of METTL3 in OC.Results: We found that METTL3 and MALAT1 were significantly overexpressed in OC tissues and cells compared to normal ovarian tissues and cells. The proliferation rate of OC cells was reduced significantly after knocking down the expression of METTL3 or MALAT1. Subsequently, MALAT1 as oncogene was found to interact with METTL3 and was upregulated in OC tissues and cells. Silencing MALAT1 inhibited OC cell proliferation. Further studies indicated that METTL3 enhanced the stability of MALAT1 by promoting the m6A modification of MALAT1 and that ELAVL1 as a downstream binding protein significantly up-regulated MALAT1 expression.Conclusion: In conclusion, METTL3 was a carcinogenic molecule that promoted the occurrence of OC. The potential mechanism of the carcinogenic effect of METTL3 was realized by enhancing the m6A modification of MALAT1 mRNA through RNA binding protein ELAVL1.Keywords: N6-methyladenosine, ovarian cancer, METTL3, MALAT1

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