m6A methyltransferase METTL3-mediated lncRNA FOXD2-AS1 promotes the tumorigenesis of cervical cancer

Fei Ji; Yang Lu; Shaoyun Chen; Xiaoling Lin; Yan Yu; Yuanfang Zhu; Xin Luo

Molecular Therapy: Oncolytics (Sep 2021)

m6A methyltransferase METTL3-mediated lncRNA FOXD2-AS1 promotes the tumorigenesis of cervical cancer

Fei Ji,
Yang Lu,
Shaoyun Chen,
Xiaoling Lin,
Yan Yu,
Yuanfang Zhu,
Xin Luo

Affiliations

Fei Ji: Department of Obstetrics and Gynecology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen 518102, China; The First Clinical Medical College of Jinan University, Guangzhou 510632, China
Yang Lu: Department of Obstetrics and Gynecology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen 518102, China
Shaoyun Chen: Maternal-Fetal Medicine Institute, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen 518102, China
Xiaoling Lin: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
Yan Yu: Department of Obstetrics and Gynecology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen 518102, China
Yuanfang Zhu: Department of Obstetrics and Gynecology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen 518102, China; Corresponding author: Yuanfang Zhu, Department of Obstetrics and Gynecology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen 518102, China.
Xin Luo: The First Clinical Medical College of Jinan University, Guangzhou 510632, China; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China; Corresponding author: Xin Luo, The First Clinical Medical College of Jinan University, Guangzhou 510632, China.

Journal volume & issue: Vol. 22
pp. 574 – 581

Abstract

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Recent studies have indicated that long noncoding RNA (lncRNA) and N6-methyladenosine (m6A) methylation modification play critical roles in human cancers; however, their regulation on cervical cancer is largely unclear. Here, our study tries to investigate the underlying mechanisms by which lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) modulates cervical cancer tumorigenesis. Results illuminated that FOXD2-AS1 expression was significantly upregulated in cervical cancer cells and tissue, which was closely correlated to the unfavorable prognosis. Functionally, gain and loss-of-function assays showed that FOXD2-AS1 promoted the migration and proliferation of cervical cancer cells. Besides, FOXD2-AS1 silencing repressed the tumor growth in vivo. Mechanistically, m6A methyltransferase methyltransferase-like 3 (METTL3) enhanced the stability of FOXD2-AS1 and maintained its expression. Moreover, FOXD2-AS1 recruited lysine-specific demethylase 1 (LSD1) to the promoter region of p21 to silence its transcription abundance. In conclusion, these findings support that METTL3/FOXD2-AS1 accelerates cervical cancer progression via a m6A-dependent modality, which may serve as a potential therapeutic target for cervical cancer.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

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