METTL3 Promotes the Growth and Invasion of Melanoma Cells by Regulating the lncRNA SNHG3/miR-330-5p Axis

Accumulating evidence indicates that m 6 A methyltransferase 3 (METTL3) plays a pivotal role in different malignancies including melanoma. However, the function and underlying mechanisms by which METTL3 contributes to the tumorigenesis of melanoma remain undocumented. The association of METTL3 and l...

Full description

Bibliographic Details
Main Authors: Shaojun Chu, Yulong Li, Baojin Wu, Guo Rong, Qiang Hou, Qin Zhou, Dexiang Du, Yufei Li
Format: Article
Language:English
Published: SAGE Publishing 2023-08-01
Series:Cell Transplantation
Online Access:https://doi.org/10.1177/09636897231188300
_version_ 1797733391300296704
author Shaojun Chu
Yulong Li
Baojin Wu
Guo Rong
Qiang Hou
Qin Zhou
Dexiang Du
Yufei Li
author_facet Shaojun Chu
Yulong Li
Baojin Wu
Guo Rong
Qiang Hou
Qin Zhou
Dexiang Du
Yufei Li
author_sort Shaojun Chu
collection DOAJ
description Accumulating evidence indicates that m 6 A methyltransferase 3 (METTL3) plays a pivotal role in different malignancies including melanoma. However, the function and underlying mechanisms by which METTL3 contributes to the tumorigenesis of melanoma remain undocumented. The association of METTL3 and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) with clinicopathological characteristics and prognosis in patients with melanoma was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and The Cancer Genome Atlas data sets. The role of METTL3 in melanoma cells was assessed by in vitro and in vivo experiments. The m 6 A dot blot, methylated RNA immunoprecipitation (MeRIP), and RT-qPCR were used to verify METTL3-mediated m 6 A modification of lncRNA SNHG3. The effect of METTL3 on lncRNA SNHG3 was determined by luciferase gene reporter assay, RT-qPCR, and Western blotting. We found that METTL3 was upregulated in melanoma tissue samples and associated with poor survival in patients with melanoma. Knockdown of METTL3 suppressed the growth and invasion of melanoma cells in vitro and in vivo , whereas restored expression of METTL3 promoted these effects. Mechanistic investigations showed that knockdown of METTL3 reduced SNHG3 m 6 A levels and its messenger ribonucleic acid (mRNA) expression levels. SNHG3 could act as a sponge of microRNA (miR)-330-5p to upregulate the expression of CCHC-type zinc finger nucleic acid binding protein (CNBP). SNHG3 overexpression reversed METTL3-knockdown-caused antitumor effects, miR-330-5p upregulation and CNBP downregulation. SNHG3 had a positive correlation with METTL3 expression but a negative correlation with miR-330-5p expression in melanoma tissue samples. In conclusion, our findings demonstrated that METTL3-mediated m 6 A modification of lncRNA SNHG3 promoted the growth and invasion of melanoma cells by regulating the miR-330-5p/CNBP axis.
first_indexed 2024-03-12T12:28:26Z
format Article
id doaj.art-20829921628741bc96990312cf58d251
institution Directory Open Access Journal
issn 1555-3892
language English
last_indexed 2024-03-12T12:28:26Z
publishDate 2023-08-01
publisher SAGE Publishing
record_format Article
series Cell Transplantation
spelling doaj.art-20829921628741bc96990312cf58d2512023-08-29T18:41:44ZengSAGE PublishingCell Transplantation1555-38922023-08-013210.1177/09636897231188300METTL3 Promotes the Growth and Invasion of Melanoma Cells by Regulating the lncRNA SNHG3/miR-330-5p AxisShaojun Chu0Yulong Li1Baojin Wu2Guo Rong3Qiang Hou4Qin Zhou5Dexiang Du6Yufei Li7Department of Plastic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Military Medical Psychology, Air Force Medical University, Xi’an, ChinaDepartment of Plastic Surgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Plastic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Plastic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Plastic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Plastic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Plastic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaAccumulating evidence indicates that m 6 A methyltransferase 3 (METTL3) plays a pivotal role in different malignancies including melanoma. However, the function and underlying mechanisms by which METTL3 contributes to the tumorigenesis of melanoma remain undocumented. The association of METTL3 and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) with clinicopathological characteristics and prognosis in patients with melanoma was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and The Cancer Genome Atlas data sets. The role of METTL3 in melanoma cells was assessed by in vitro and in vivo experiments. The m 6 A dot blot, methylated RNA immunoprecipitation (MeRIP), and RT-qPCR were used to verify METTL3-mediated m 6 A modification of lncRNA SNHG3. The effect of METTL3 on lncRNA SNHG3 was determined by luciferase gene reporter assay, RT-qPCR, and Western blotting. We found that METTL3 was upregulated in melanoma tissue samples and associated with poor survival in patients with melanoma. Knockdown of METTL3 suppressed the growth and invasion of melanoma cells in vitro and in vivo , whereas restored expression of METTL3 promoted these effects. Mechanistic investigations showed that knockdown of METTL3 reduced SNHG3 m 6 A levels and its messenger ribonucleic acid (mRNA) expression levels. SNHG3 could act as a sponge of microRNA (miR)-330-5p to upregulate the expression of CCHC-type zinc finger nucleic acid binding protein (CNBP). SNHG3 overexpression reversed METTL3-knockdown-caused antitumor effects, miR-330-5p upregulation and CNBP downregulation. SNHG3 had a positive correlation with METTL3 expression but a negative correlation with miR-330-5p expression in melanoma tissue samples. In conclusion, our findings demonstrated that METTL3-mediated m 6 A modification of lncRNA SNHG3 promoted the growth and invasion of melanoma cells by regulating the miR-330-5p/CNBP axis.https://doi.org/10.1177/09636897231188300
spellingShingle Shaojun Chu
Yulong Li
Baojin Wu
Guo Rong
Qiang Hou
Qin Zhou
Dexiang Du
Yufei Li
METTL3 Promotes the Growth and Invasion of Melanoma Cells by Regulating the lncRNA SNHG3/miR-330-5p Axis
Cell Transplantation
title METTL3 Promotes the Growth and Invasion of Melanoma Cells by Regulating the lncRNA SNHG3/miR-330-5p Axis
title_full METTL3 Promotes the Growth and Invasion of Melanoma Cells by Regulating the lncRNA SNHG3/miR-330-5p Axis
title_fullStr METTL3 Promotes the Growth and Invasion of Melanoma Cells by Regulating the lncRNA SNHG3/miR-330-5p Axis
title_full_unstemmed METTL3 Promotes the Growth and Invasion of Melanoma Cells by Regulating the lncRNA SNHG3/miR-330-5p Axis
title_short METTL3 Promotes the Growth and Invasion of Melanoma Cells by Regulating the lncRNA SNHG3/miR-330-5p Axis
title_sort mettl3 promotes the growth and invasion of melanoma cells by regulating the lncrna snhg3 mir 330 5p axis
url https://doi.org/10.1177/09636897231188300
work_keys_str_mv AT shaojunchu mettl3promotesthegrowthandinvasionofmelanomacellsbyregulatingthelncrnasnhg3mir3305paxis
AT yulongli mettl3promotesthegrowthandinvasionofmelanomacellsbyregulatingthelncrnasnhg3mir3305paxis
AT baojinwu mettl3promotesthegrowthandinvasionofmelanomacellsbyregulatingthelncrnasnhg3mir3305paxis
AT guorong mettl3promotesthegrowthandinvasionofmelanomacellsbyregulatingthelncrnasnhg3mir3305paxis
AT qianghou mettl3promotesthegrowthandinvasionofmelanomacellsbyregulatingthelncrnasnhg3mir3305paxis
AT qinzhou mettl3promotesthegrowthandinvasionofmelanomacellsbyregulatingthelncrnasnhg3mir3305paxis
AT dexiangdu mettl3promotesthegrowthandinvasionofmelanomacellsbyregulatingthelncrnasnhg3mir3305paxis
AT yufeili mettl3promotesthegrowthandinvasionofmelanomacellsbyregulatingthelncrnasnhg3mir3305paxis