LncRNA TCL6 regulates miR-876–5p/MYL2 axis to suppress breast cancer progression

We explored the influence of the TCL6/miR-876–5p axis on breast cancer cell proliferation and migration. Using The Cancer Genome Atlas (TCGA) database, we evaluated the expression of TCL6 in breast cancer patients and studied its effects on cell proliferation, migration, and the cell cycle in vitro....

Full description

Saved in:
Bibliographic Details
Main Authors: YaoBang Liu, Hong Li, DaHai Chai, Bin Lian, ZhengYang Bai, YaLi Gao, JinPing Li
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Translational Oncology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1936523324003371
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850230755860414464
author YaoBang Liu
Hong Li
DaHai Chai
Bin Lian
ZhengYang Bai
YaLi Gao
JinPing Li
author_facet YaoBang Liu
Hong Li
DaHai Chai
Bin Lian
ZhengYang Bai
YaLi Gao
JinPing Li
author_sort YaoBang Liu
collection DOAJ
description We explored the influence of the TCL6/miR-876–5p axis on breast cancer cell proliferation and migration. Using The Cancer Genome Atlas (TCGA) database, we evaluated the expression of TCL6 in breast cancer patients and studied its effects on cell proliferation, migration, and the cell cycle in vitro. The regulatory effect of miR-876–5p on myosin light chain-2 (MYL2) 3′ untranslated regions (3′UTR) was analyzed through luciferase reporter assays, and rescue experiments confirmed TCL6-driven upregulation of MYL2 via a competitive RNA binding mechanism. Furthermore, we used a mouse subcutaneous tumor model to assess the impact of TCL6 knockdown combined with immune checkpoint blockade therapy. Our results indicated that higher TCL6 expression correlated with a favorable prognosis in breast cancer patients. In vitro experiments showed that knockdown of TCL6 and MYL2 enhanced breast cancer cell proliferation and migration. The luciferase and rescue assays demonstrated that TCL6 interacted with miR-876–5p to upregulate MYL2, thereby inhibiting cell proliferation and migration. Both in vitro and in vivo studies revealed that overexpression of TCL6 suppressed tumor growth and improved the response to PD-1 immunotherapy in tumor-bearing mice. This research highlights the pivotal role of lncRNA TCL6 in breast cancer development via a ceRNA network involving miR-876–5p and MYL2, suggesting a novel molecular target for breast cancer therapy.
format Article
id doaj-art-eacc97d715d146839dccfd23cd8de584
institution OA Journals
issn 1936-5233
language English
publishDate 2025-03-01
publisher Elsevier
record_format Article
series Translational Oncology
spelling doaj-art-eacc97d715d146839dccfd23cd8de5842025-08-20T02:03:46ZengElsevierTranslational Oncology1936-52332025-03-015310221010.1016/j.tranon.2024.102210LncRNA TCL6 regulates miR-876–5p/MYL2 axis to suppress breast cancer progressionYaoBang Liu0Hong Li1DaHai Chai2Bin Lian3ZhengYang Bai4YaLi Gao5JinPing Li6Department of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaDepartment of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaDepartment of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaDepartment of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaNingxia Medical University, Yinchuan 750004, ChinaNingxia Medical University, Yinchuan 750004, ChinaDepartment of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, China; Corresponding author.We explored the influence of the TCL6/miR-876–5p axis on breast cancer cell proliferation and migration. Using The Cancer Genome Atlas (TCGA) database, we evaluated the expression of TCL6 in breast cancer patients and studied its effects on cell proliferation, migration, and the cell cycle in vitro. The regulatory effect of miR-876–5p on myosin light chain-2 (MYL2) 3′ untranslated regions (3′UTR) was analyzed through luciferase reporter assays, and rescue experiments confirmed TCL6-driven upregulation of MYL2 via a competitive RNA binding mechanism. Furthermore, we used a mouse subcutaneous tumor model to assess the impact of TCL6 knockdown combined with immune checkpoint blockade therapy. Our results indicated that higher TCL6 expression correlated with a favorable prognosis in breast cancer patients. In vitro experiments showed that knockdown of TCL6 and MYL2 enhanced breast cancer cell proliferation and migration. The luciferase and rescue assays demonstrated that TCL6 interacted with miR-876–5p to upregulate MYL2, thereby inhibiting cell proliferation and migration. Both in vitro and in vivo studies revealed that overexpression of TCL6 suppressed tumor growth and improved the response to PD-1 immunotherapy in tumor-bearing mice. This research highlights the pivotal role of lncRNA TCL6 in breast cancer development via a ceRNA network involving miR-876–5p and MYL2, suggesting a novel molecular target for breast cancer therapy.http://www.sciencedirect.com/science/article/pii/S1936523324003371Breast cancerLncrna tcl6Prognostic analysisCerna networkImmune responseTumor growth
spellingShingle YaoBang Liu
Hong Li
DaHai Chai
Bin Lian
ZhengYang Bai
YaLi Gao
JinPing Li
LncRNA TCL6 regulates miR-876–5p/MYL2 axis to suppress breast cancer progression
Translational Oncology
Breast cancer
Lncrna tcl6
Prognostic analysis
Cerna network
Immune response
Tumor growth
title LncRNA TCL6 regulates miR-876–5p/MYL2 axis to suppress breast cancer progression
title_full LncRNA TCL6 regulates miR-876–5p/MYL2 axis to suppress breast cancer progression
title_fullStr LncRNA TCL6 regulates miR-876–5p/MYL2 axis to suppress breast cancer progression
title_full_unstemmed LncRNA TCL6 regulates miR-876–5p/MYL2 axis to suppress breast cancer progression
title_short LncRNA TCL6 regulates miR-876–5p/MYL2 axis to suppress breast cancer progression
title_sort lncrna tcl6 regulates mir 876 5p myl2 axis to suppress breast cancer progression
topic Breast cancer
Lncrna tcl6
Prognostic analysis
Cerna network
Immune response
Tumor growth
url http://www.sciencedirect.com/science/article/pii/S1936523324003371
work_keys_str_mv AT yaobangliu lncrnatcl6regulatesmir8765pmyl2axistosuppressbreastcancerprogression
AT hongli lncrnatcl6regulatesmir8765pmyl2axistosuppressbreastcancerprogression
AT dahaichai lncrnatcl6regulatesmir8765pmyl2axistosuppressbreastcancerprogression
AT binlian lncrnatcl6regulatesmir8765pmyl2axistosuppressbreastcancerprogression
AT zhengyangbai lncrnatcl6regulatesmir8765pmyl2axistosuppressbreastcancerprogression
AT yaligao lncrnatcl6regulatesmir8765pmyl2axistosuppressbreastcancerprogression
AT jinpingli lncrnatcl6regulatesmir8765pmyl2axistosuppressbreastcancerprogression