Knockdown of long noncoding RNA TP73-AS1 suppresses the malignant progression of breast cancer cells in vitro through targeting miRNA-125a-3p/metadherin axis

Autor: Qian Ma, Yuxiong Liu, Yanyan Han, Guangqing Wei
Rok vydání: 2019
Předmět:
0301 basic medicine
Apoptosis
medicine.disease_cause
Mice
0302 clinical medicine
Breast cancer
TP73‐AS1
Cell Movement
Tumor Cells
Cultured
Medicine
Gene knockdown
Mice
Inbred BALB C
RNA-Binding Proteins
MTDH
General Medicine
malignant progression
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Antisense RNA
Gene Expression Regulation
Neoplastic
Oncology
030220 oncology & carcinogenesis
Disease Progression
Female
RNA
Long Noncoding
Original Article
Pulmonary and Respiratory Medicine
miR‐125a
Mice
Nude
Breast Neoplasms
In Vitro Techniques
lcsh:RC254-282
03 medical and health sciences
Downregulation and upregulation
microRNA
Biomarkers
Tumor
Gene silencing
Animals
Humans
Cell Proliferation
business.industry
Cell growth
Membrane Proteins
Original Articles
Xenograft Model Antitumor Assays
MicroRNAs
030104 developmental biology
Cancer research
business
Carcinogenesis
Zdroj: Thoracic Cancer
Thoracic Cancer, Vol 11, Iss 2, Pp 394-407 (2020)
ISSN: 1759-7714
Popis: Background TP73 antisense RNA 1 (TP73‐AS1) is a long noncoding RNA which has been shown to be involved in the progression of multiple malignant tumors. Previous studies have demonstrated the oncogenic role of TP73‐AS1 in breast cancer. However, its molecular mechanism remains largely unknown in breast tumorigenesis. Methods Expression of TP63‐AS1, miRNA‐125a‐3p (miR‐125a) and metadherin (MTDH) was detected by real‐time quantitative PCR and western blotting. The malignancy was evaluated by cell counting kit 8 (CCK‐8), transwell assays, flow cytometry and western blotting. The target binding was confirmed by dual luciferase reporter assay. Xenograft tumor model was performed to detect tumor growth in vivo. Results Expression of TP73‐AS1 was higher in breast cancer tissues and cell lines. Biologically, its knockdown could promote cell apoptosis rate, and inhibit proliferative capacity, migration and invasion ability in HCC‐70 and MB231 cells, accompanied with higher cleaved caspase 3 level and lower Ki67, N‐cadherin and Vimentin level. Moreover, TP73‐AS1 downregulation restrained the tumor growth of HCC‐70 cells in vivo. Mechanically, TP73‐AS1 functioned as a molecular “sponge” for miR‐125a to modulate MTDH, a downstream target of miR‐125a. Intriguingly, both miR‐125a overexpression and MTDH silencing exerted a tumor‐suppressive effect in the malignant progression of HCC‐70 and MB231 cells, which was counteracted by TP73‐AS1 upregulation and miR‐125a downregulation, respectively. Conclusion Knockdown of TP73‐AS1 inhibited cell proliferation, migration and invasion, but facilitated apoptosis in breast cancer cells in vitro through targeting miR‐125a and upregulating MTDH, suggesting a novel TP73‐AS1/miR‐125a/MTDH pathway in the malignant progression of breast cancer.
Databáze: OpenAIRE
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