Promoter A1312C mutation leads to microRNA-7 downregulation in human non-small cell lung cancer
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
MicroRNA-7 (miRNA-7, miR-7) is a unique class of tumor suppressors, plays an important role in various physiological and pathological processes including human non-small cell lung cancer (NSCLC). In previous works, we revealed that miR-7 could regulate the growth and metastasis of human NSCLC cells. However, the mechanism of dysregulated miR-7 expression in NSCLC remains to be further elucidated. In this study, based on clinical sample analysis, we found that the downregulated expression of miR-7 was dominantly attributed to the decreased level of pri-miR-7-2 in human NSCLC. Furthermore, there were four site mutations in the miR-7-2 promoter sequence. Notably, among these four sites, mutation at -1312 locus (A → C, termed as A1312C mutation) was dominate, and A1312C mutation further led to decreased expression of miR-7 in human NSCLC cells, accompanied with elevated transduction of NDUFA4/ERK/AKT signaling pathway. Mechanistically, homeobox A5 (HOXA5) is the key transcription factors regulating miR-7 expression in NSCLC. A1312C mutation impairs HOXA5 binding, thereby reducing the transcriptional activity of miR-7-2 promoter, resulting in downregulation of miR-7 expression. Together, these data may provide new insights into the dysregulation of specific miRNA expression in NSCLC and ultimately prove to be helpful in the diagnostic, prognostic, and therapeutic strategies against NSCLC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:117 |
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| Enthalten in: |
Cellular signalling - 117(2024) vom: 01. März, Seite 111095 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Shipeng [VerfasserIn] |
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| Links: |
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| Themen: |
AKT |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cellsig.2024.111095 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368366618 |
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a MicroRNA-7 (miRNA-7, miR-7) is a unique class of tumor suppressors, plays an important role in various physiological and pathological processes including human non-small cell lung cancer (NSCLC). In previous works, we revealed that miR-7 could regulate the growth and metastasis of human NSCLC cells. However, the mechanism of dysregulated miR-7 expression in NSCLC remains to be further elucidated. In this study, based on clinical sample analysis, we found that the downregulated expression of miR-7 was dominantly attributed to the decreased level of pri-miR-7-2 in human NSCLC. Furthermore, there were four site mutations in the miR-7-2 promoter sequence. Notably, among these four sites, mutation at -1312 locus (A → C, termed as A1312C mutation) was dominate, and A1312C mutation further led to decreased expression of miR-7 in human NSCLC cells, accompanied with elevated transduction of NDUFA4/ERK/AKT signaling pathway. Mechanistically, homeobox A5 (HOXA5) is the key transcription factors regulating miR-7 expression in NSCLC. A1312C mutation impairs HOXA5 binding, thereby reducing the transcriptional activity of miR-7-2 promoter, resulting in downregulation of miR-7 expression. Together, these data may provide new insights into the dysregulation of specific miRNA expression in NSCLC and ultimately prove to be helpful in the diagnostic, prognostic, and therapeutic strategies against NSCLC | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Wang, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Mengmeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xu |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Longqing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Juanjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Lin |e verfasserin |4 aut | |
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