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...
Guardado en:
Autores principales: | , , , , , , , |
---|---|
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 |