miRNA‐449c‐5p regulates the JAK‐STAT pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting ERBB2

Abstract Background Breast cancer is a highly prevalent disease worldwide, and early diagnosis and treatment could reduce the mortality rate of breast cancer patients. microRNAs (miRNA) have been shown to regulate the occurrences and progression of many types of cancers. Thus, it is crucial to find...

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Main Authors: Li Li, Yangqiurong Zhang, Kunxian Yang, Wei Liu, Ziting Zhou, Ying Xu
Format: Article
Language:English
Published: Wiley 2024-02-01
Series:Cancer Reports
Subjects:
Online Access:https://doi.org/10.1002/cnr2.1974
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author Li Li
Yangqiurong Zhang
Kunxian Yang
Wei Liu
Ziting Zhou
Ying Xu
author_facet Li Li
Yangqiurong Zhang
Kunxian Yang
Wei Liu
Ziting Zhou
Ying Xu
author_sort Li Li
collection DOAJ
description Abstract Background Breast cancer is a highly prevalent disease worldwide, and early diagnosis and treatment could reduce the mortality rate of breast cancer patients. microRNAs (miRNA) have been shown to regulate the occurrences and progression of many types of cancers. Thus, it is crucial to find novel biomarkers in breast cancer. miR‐449c‐5p acted as a biomarker in non‐small cell lung cancer, gastric carcinoma, and so forth. ERBB2 is an ideal target for breast cancer therapy. However, the molecular mechanisms between miR‐449c‐5p and ERBB2 in breast cancer remain poorly understood. Our study focused on the regulatory role of miR‐449c‐5p in breast cancer and its targeting relationship with ERBB2. Methods The miR‐449c‐5p expression in breast cancer tissue and normal tissue was searched from the online database (Starbase). The clinical prognosis of miR‐449c‐5p and ERBB2 was predicted by using the Kaplan–Meier analysis method. The expression of miR‐449c‐5p mimics and inhibitors was measured by qRT‐PCR. T47D cells were transfected with miR‐449c‐5p mimics and miR‐449c‐5p inhibitors. After that, CCK‐8, colony formation assays and Transwell assays were used to evaluate the cell proliferation ability, migration and invasion. Whether ERBB2 was the target gene of the miR‐449c‐5p was predicted by Starbase and verified by dual‐luciferase activity assay. In addition, protein levels and the relationship between signalling pathways were measured and validated using western blotting analysis. Results We confirmed that miR‐449c‐5p was highly expressed in breast cancer tissue, and its downregulation was linked with poor prognosis. Overexpression of miR‐449c‐5p inhibited the proliferation, migration and invasion of breast cancer cells. ERBB2 was a target of miR‐449c‐5p. The invasion, migration, and proliferation of breast cancer cells were inhibited by miR‐449c‐5p/ERBB2 through JAK‐STAT. Conclusion This study demonstrated that miR‐449c‐5p inhibits breast cancer cell proliferation, migration and invasion by targeting ERBB2 via JAK/STAT, which means miR‐449c‐5p, is a potential biomarker for breast cancer and provides a novel insight for diagnosis.
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spelling doaj.art-c1332b9cdd4a4233b6e27db4ae5be9222024-02-28T13:54:58ZengWileyCancer Reports2573-83482024-02-0172n/an/a10.1002/cnr2.1974miRNA‐449c‐5p regulates the JAK‐STAT pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting ERBB2Li Li0Yangqiurong Zhang1Kunxian Yang2Wei Liu3Ziting Zhou4Ying Xu5Department of Breast and Thyroid Surgery The First People's Hospital of Yunnan Province, The Affiliated Hospital of Medical College, Kunming University of Science and Technology Kunming ChinaDepartment of Breast and Thyroid Surgery The First People's Hospital of Yunnan Province, The Affiliated Hospital of Medical College, Kunming University of Science and Technology Kunming ChinaDepartment of Breast and Thyroid Surgery The First People's Hospital of Yunnan Province, The Affiliated Hospital of Medical College, Kunming University of Science and Technology Kunming ChinaDepartment of Breast and Thyroid Surgery The First People's Hospital of Yunnan Province, The Affiliated Hospital of Medical College, Kunming University of Science and Technology Kunming ChinaDepartment of Breast and Thyroid Surgery The First People's Hospital of Yunnan Province, The Affiliated Hospital of Medical College, Kunming University of Science and Technology Kunming ChinaDepartment of Breast and Thyroid Surgery The First People's Hospital of Yunnan Province, The Affiliated Hospital of Medical College, Kunming University of Science and Technology Kunming ChinaAbstract Background Breast cancer is a highly prevalent disease worldwide, and early diagnosis and treatment could reduce the mortality rate of breast cancer patients. microRNAs (miRNA) have been shown to regulate the occurrences and progression of many types of cancers. Thus, it is crucial to find novel biomarkers in breast cancer. miR‐449c‐5p acted as a biomarker in non‐small cell lung cancer, gastric carcinoma, and so forth. ERBB2 is an ideal target for breast cancer therapy. However, the molecular mechanisms between miR‐449c‐5p and ERBB2 in breast cancer remain poorly understood. Our study focused on the regulatory role of miR‐449c‐5p in breast cancer and its targeting relationship with ERBB2. Methods The miR‐449c‐5p expression in breast cancer tissue and normal tissue was searched from the online database (Starbase). The clinical prognosis of miR‐449c‐5p and ERBB2 was predicted by using the Kaplan–Meier analysis method. The expression of miR‐449c‐5p mimics and inhibitors was measured by qRT‐PCR. T47D cells were transfected with miR‐449c‐5p mimics and miR‐449c‐5p inhibitors. After that, CCK‐8, colony formation assays and Transwell assays were used to evaluate the cell proliferation ability, migration and invasion. Whether ERBB2 was the target gene of the miR‐449c‐5p was predicted by Starbase and verified by dual‐luciferase activity assay. In addition, protein levels and the relationship between signalling pathways were measured and validated using western blotting analysis. Results We confirmed that miR‐449c‐5p was highly expressed in breast cancer tissue, and its downregulation was linked with poor prognosis. Overexpression of miR‐449c‐5p inhibited the proliferation, migration and invasion of breast cancer cells. ERBB2 was a target of miR‐449c‐5p. The invasion, migration, and proliferation of breast cancer cells were inhibited by miR‐449c‐5p/ERBB2 through JAK‐STAT. Conclusion This study demonstrated that miR‐449c‐5p inhibits breast cancer cell proliferation, migration and invasion by targeting ERBB2 via JAK/STAT, which means miR‐449c‐5p, is a potential biomarker for breast cancer and provides a novel insight for diagnosis.https://doi.org/10.1002/cnr2.1974breast cancerERBB2JAK/STAT signalingmiR‐449c‐5p
spellingShingle Li Li
Yangqiurong Zhang
Kunxian Yang
Wei Liu
Ziting Zhou
Ying Xu
miRNA‐449c‐5p regulates the JAK‐STAT pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting ERBB2
Cancer Reports
breast cancer
ERBB2
JAK/STAT signaling
miR‐449c‐5p
title miRNA‐449c‐5p regulates the JAK‐STAT pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting ERBB2
title_full miRNA‐449c‐5p regulates the JAK‐STAT pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting ERBB2
title_fullStr miRNA‐449c‐5p regulates the JAK‐STAT pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting ERBB2
title_full_unstemmed miRNA‐449c‐5p regulates the JAK‐STAT pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting ERBB2
title_short miRNA‐449c‐5p regulates the JAK‐STAT pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting ERBB2
title_sort mirna 449c 5p regulates the jak stat pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting erbb2
topic breast cancer
ERBB2
JAK/STAT signaling
miR‐449c‐5p
url https://doi.org/10.1002/cnr2.1974
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