Mechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer

Methyltransferase like 3 (METTL3) has been identified to serve as a definitive inducer in cancer progression. This study sought to analyze the regulatory mechanism of METTL3 in epithelial-mesenchymal transition (EMT), invasion, and metastasis in esophageal cancer (ESCA). The METTL3 expressions in ca...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Xuyang Liang, Zhimei Zhang, Lu Wang, Shuxian Zhang, Ling Ren, Shouying Li, Jing Xu, Shengxiang Lv
Formato: article
Lenguaje:EN
Publicado: Taylor & Francis Group 2021
Materias:
Acceso en línea:https://doaj.org/article/83461020d9fb4d3f82151f336aa10945
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:83461020d9fb4d3f82151f336aa10945
record_format dspace
spelling oai:doaj.org-article:83461020d9fb4d3f82151f336aa109452021-12-01T14:41:00ZMechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer2165-59792165-598710.1080/21655979.2021.1994721https://doaj.org/article/83461020d9fb4d3f82151f336aa109452021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1994721https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Methyltransferase like 3 (METTL3) has been identified to serve as a definitive inducer in cancer progression. This study sought to analyze the regulatory mechanism of METTL3 in epithelial-mesenchymal transition (EMT), invasion, and metastasis in esophageal cancer (ESCA). The METTL3 expressions in cancer tissues and cells were detected with extensive analysis of its correlation with clinical baseline data. The cells were transfected with sh-RNA-METTL3 and microRNA (miR)-20a-5p mimic, followed by evaluation of invasion, migration, and EMT. The N6-methyladenosine (m6A) level and enrichment of DiGeorge Critical Region 8 (DGCR8) and m6A were observed. The binding relationship between miR-20a-5p and Nuclear Factor I-C (NFIC) was verified, followed by Pearson correlation analysis. A subcutaneous tumor formation assay was conducted prior to observation of lung metastases. Our results revealed that METTL3 was highly expressed in ESCA patients and associated with severe lymph node involvement and distant metastasis. METTL3 downregulation radically inhibited the invasiveness, migration, and EMT. METTL3 elevated the miR-20a-5p expression via improving m6A modification. METTL3 inhibition downregulated the miR-20a-5p expression. Moreover, miR-20a-5p upregulation facilitated ESCA cell invasiveness and migration by targeting NFIC transcription. METTL3 inhibition suppressed tumor growth and lung metastasis in vivo. Overall, METTL3 promoted m6A modification and the binding of DGCR8 to miR-20a-5p to further elevate the miR-20a-5p expression and inhibit NFIC transcription, thus promoting EMT, invasion and migration.Xuyang LiangZhimei ZhangLu WangShuxian ZhangLing RenShouying LiJing XuShengxiang LvTaylor & Francis Grouparticleesophageal cancermettl3m6a modificationdgcr8pri-mir-20a-5pmir-20a-5pnficepithelial-mesenchymal transitionBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 10023-10036 (2021)
institution DOAJ
collection DOAJ
language EN
topic esophageal cancer
mettl3
m6a modification
dgcr8
pri-mir-20a-5p
mir-20a-5p
nfic
epithelial-mesenchymal transition
Biotechnology
TP248.13-248.65
spellingShingle esophageal cancer
mettl3
m6a modification
dgcr8
pri-mir-20a-5p
mir-20a-5p
nfic
epithelial-mesenchymal transition
Biotechnology
TP248.13-248.65
Xuyang Liang
Zhimei Zhang
Lu Wang
Shuxian Zhang
Ling Ren
Shouying Li
Jing Xu
Shengxiang Lv
Mechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer
description Methyltransferase like 3 (METTL3) has been identified to serve as a definitive inducer in cancer progression. This study sought to analyze the regulatory mechanism of METTL3 in epithelial-mesenchymal transition (EMT), invasion, and metastasis in esophageal cancer (ESCA). The METTL3 expressions in cancer tissues and cells were detected with extensive analysis of its correlation with clinical baseline data. The cells were transfected with sh-RNA-METTL3 and microRNA (miR)-20a-5p mimic, followed by evaluation of invasion, migration, and EMT. The N6-methyladenosine (m6A) level and enrichment of DiGeorge Critical Region 8 (DGCR8) and m6A were observed. The binding relationship between miR-20a-5p and Nuclear Factor I-C (NFIC) was verified, followed by Pearson correlation analysis. A subcutaneous tumor formation assay was conducted prior to observation of lung metastases. Our results revealed that METTL3 was highly expressed in ESCA patients and associated with severe lymph node involvement and distant metastasis. METTL3 downregulation radically inhibited the invasiveness, migration, and EMT. METTL3 elevated the miR-20a-5p expression via improving m6A modification. METTL3 inhibition downregulated the miR-20a-5p expression. Moreover, miR-20a-5p upregulation facilitated ESCA cell invasiveness and migration by targeting NFIC transcription. METTL3 inhibition suppressed tumor growth and lung metastasis in vivo. Overall, METTL3 promoted m6A modification and the binding of DGCR8 to miR-20a-5p to further elevate the miR-20a-5p expression and inhibit NFIC transcription, thus promoting EMT, invasion and migration.
format article
author Xuyang Liang
Zhimei Zhang
Lu Wang
Shuxian Zhang
Ling Ren
Shouying Li
Jing Xu
Shengxiang Lv
author_facet Xuyang Liang
Zhimei Zhang
Lu Wang
Shuxian Zhang
Ling Ren
Shouying Li
Jing Xu
Shengxiang Lv
author_sort Xuyang Liang
title Mechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer
title_short Mechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer
title_full Mechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer
title_fullStr Mechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer
title_full_unstemmed Mechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer
title_sort mechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/83461020d9fb4d3f82151f336aa10945
work_keys_str_mv AT xuyangliang mechanismofmethyltransferaselike3inepithelialmesenchymaltransitionprocessinvasionandmetastasisinesophagealcancer
AT zhimeizhang mechanismofmethyltransferaselike3inepithelialmesenchymaltransitionprocessinvasionandmetastasisinesophagealcancer
AT luwang mechanismofmethyltransferaselike3inepithelialmesenchymaltransitionprocessinvasionandmetastasisinesophagealcancer
AT shuxianzhang mechanismofmethyltransferaselike3inepithelialmesenchymaltransitionprocessinvasionandmetastasisinesophagealcancer
AT lingren mechanismofmethyltransferaselike3inepithelialmesenchymaltransitionprocessinvasionandmetastasisinesophagealcancer
AT shouyingli mechanismofmethyltransferaselike3inepithelialmesenchymaltransitionprocessinvasionandmetastasisinesophagealcancer
AT jingxu mechanismofmethyltransferaselike3inepithelialmesenchymaltransitionprocessinvasionandmetastasisinesophagealcancer
AT shengxianglv mechanismofmethyltransferaselike3inepithelialmesenchymaltransitionprocessinvasionandmetastasisinesophagealcancer
_version_ 1718405003763253248