LINC00514 upregulates CCDC71L to Promote Cellular Process in Triple-Negative Breast Cancer by Sponging miR-6504-5p and miR-3139

Triple Negative ◽

Essential Gene ◽

Cellular Process ◽

Luciferase Reporter ◽

Flow Cytometry Analysis ◽

Abstract Background: Long noncoding RNAs (lncRNAs) have recently identified as essential gene modulators in numerous cancers. Previous studies have confirmed the oncogenic role of long intergenic nonprotein-coding RNA 00514 (LINC00514) in some cancers. Nevertheless, its biological function and mechanism remain elusive in triple-negative breast cancer (TNBC). Methods: Herein, we detected LINC00514 expression level in TNBC tissues and cells via RT-qPCR. The function of LINC00514 in TNBC cellular activities was assessed via colony formation, EdU, wound healing, transwell assays and flow cytometry analysis. Results: The binding between miR-6504-5p/miR-3139 and LINC00514/CCDC71L was validated by luciferase reporter assay. The data indicated that LINC00514 expression was increased in TNBC tissues and cells. Furthermore, it was manifested that silenced LINC00514 restrained cell proliferative, migratory and invasive abilities and accelerated cell apoptosis. In mechanism, LINC00514 was revealed to sequester miR-6504-5p and miR-3139 in TNBC cells. Furthermore, the low level of miR-6504-5p and miR-3139 was discovered in TNBC tissues and cells. Accordingly, we discovered overexpression of miR-6504-5p or miR-3139 retarded cell growth and migration in TNBC. Later, CCDC71L was recognized as a common downstream gene of miR-6504-5p and miR-3139. Rescue assay verified that overexpressed CCDC71L countervailed the inhibitive influence of LINC00514 knockdown in TNBC cellular process. Conclusion: MiR-6504-5p and miR-3139 were involved in LINC00514-mediated cellular activities through regulating CCDC71L expression, which provided a novel LINC00514/miR-6504-5p/miR-3139/CCDC71L axis in TNBC.

LINC00514 upregulates CCDC71L to promote cell proliferation, migration and invasion in triple‐negative breast cancer by sponging miR-6504-5p and miR-3139

Cancer Cell International ◽

10.1186/s12935-021-01875-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiao Luo ◽

Hui Wang

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Triple Negative ◽

Essential Gene ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Promote Cell Proliferation ◽

Abstract Background Long noncoding RNAs (lncRNAs) have recently identified as essential gene modulators in numerous cancers. Previous studies have confirmed the oncogenic role of long intergenic nonprotein-coding RNA 00514 (LINC00514) in some cancers. Nevertheless, its biological function and mechanism remain unclear in triple-negative breast cancer (TNBC). Methods Herein, we detected LINC00514 expression level in TNBC tissues and cells using RT-qPCR. The function of LINC00514 in TNBC cellular activities was assessed by colony formation, EdU, wound healing, transwell assays and flow cytometry analysis. Results The binding between miR-6504-5p/miR-3139 and LINC00514/CCDC71L was validated by luciferase reporter assay. The results indicated that LINC00514 expression was upregulated in TNBC tissues and cells. Furthermore, it was manifested that silenced LINC00514 restrained cell proliferative, migratory and invasive abilities and promoted cell apoptosis. In mechanism, LINC00514 was revealed to sequester miR-6504-5p and miR-3139 in TNBC cells. Furthermore, the low level of miR-6504-5p and miR-3139 was identified in TNBC tissues and cells. Overexpression of miR-6504-5p or miR-3139 inhibited cell growth and migration in TNBC. CCDC71L was recognized as a common downstream gene of miR-6504-5p and miR-3139. Rescue assay verified that overexpressed CCDC71L countervailed the anti-tumor influence of LINC00514 knockdown on TNBC cell proliferation, migration, invasion and apoptosis. Conclusions LINC00514 promote cell proliferation, migration and invasion in triple-negative breast cancer by targeting the miR-6504-5p/miR-3139/CCDC71L axis in TNBC.

LINC01234 aggravates cell growth and migration of triple‐negative breast cancer by activating the Wnt pathway

Environmental Toxicology ◽

10.1002/tox.23318 ◽

2021 ◽

Author(s):

Feng Xiao ◽

Hongyao Jia ◽

Di Wu ◽

Zhiru Zhang ◽

Sijie Li ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Wnt Pathway ◽

Triple Negative ◽

The Potential Prognostic Role of Oligosaccharide-Binding Fold-Containing Protein 2A (OBFC2A) in Triple-Negative Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.751430 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qianxue Wu ◽

Xin Tang ◽

Wenming Zhu ◽

Qing Li ◽

Xiang Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Candidate Genes ◽

Breast Cancer Cells ◽

Triple Negative ◽

G1 Phase ◽

BackgroundPatients with triple-negative breast cancer (TNBC) have poor overall survival. The present study aimed to investigate the potential prognostics of TNBC by analyzing breast cancer proteomic and transcriptomic datasets.MethodsCandidate proteins selected from CPTAC (the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium) were validated using datasets from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium). Kaplan-Meier analysis and ROC (receiver operating characteristic) curve analysis were performed to explore the prognosis of candidate genes. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were performed on the suspected candidate genes. Single-cell RNA-seq (scRNA-seq) data from GSE118389 were used to analyze the cell clusters in which OBFC2A (Oligosaccharide-Binding Fold-Containing Protein 2A) was mainly distributed. TIMER (Tumor Immune Estimation Resource) was used to verify the correlation between OBFC2A expression and immune infiltration. Clone formation assays and wound healing assays were used to detect the role of OBFC2A expression on the proliferation, invasion, and migration of breast cancer cells. Flow cytometry was used to analyze the effects of silencing OBFC2A on breast cancer cell cycle and apoptosis.ResultsSix candidate proteins were found to be differentially expressed in non-TNBC and TNBC groups from CPTAC. However, only OBFC2A was identified as an independently poor prognostic gene marker in METABRIC (HR=3.658, 1.881-7.114). And OBFC2A was associated with immune functions in breast cancer. Biological functional experiments showed that OBFC2A might promote the proliferation and migration of breast cancer cells. The inhibition of OBFC2A expression blocked the cell cycle in G1 phase and inhibited the transformation from G1 phase to S phase. Finally, downregulation of OBFC2A also increased the total apoptosis rate of cells.ConclusionOn this basis, OBFC2A may be a potential prognostic biomarker for TNBC.

S-Adenosylmethionine Inhibits Cell Growth and Migration of Triple Negative Breast Cancer Cells through Upregulating MiRNA-34c and MiRNA-449a

International Journal of Molecular Sciences ◽

10.3390/ijms22010286 ◽

2020 ◽

Vol 22 (1) ◽

pp. 286

Author(s):

Alessandra Coppola ◽

Concetta Paola Ilisso ◽

Antonietta Stellavato ◽

Chiara Schiraldi ◽

Michele Caraglia ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Therapy ◽

Triple Negative ◽

Time Lapse ◽

Antitumor Effects ◽

Cancer Agent ◽

Triple-negative breast cancer (TNBC) is one of the most common malignancies worldwide and shows maximum invasiveness and a high risk of metastasis. Recently, many natural compounds have been highlighted as a valuable source of new and less toxic drugs to enhance breast cancer therapy. Among them, S-adenosyl-L-methionine (AdoMet) has emerged as a promising anti-cancer agent. MicroRNA (miRNA or miR)-based gene therapy provides an interesting antitumor approach to integrated cancer therapy. In this study, we evaluated AdoMet-induced modulation of miRNA-34c and miRNA-449a expression in MDA-MB-231 and MDA-MB-468 TNBC cells. We demonstrated that AdoMet upregulates miR-34c and miR-449a expression in both cell lines. We found that the combination of AdoMet with miR-34c or miR-449a mimic strongly potentiated the pro-apoptotic effect of the sulfonium compound by a caspase-dependent mechanism. For the first time, by video time-lapse microscopy, we showed that AdoMet inhibited the in vitro migration of MDA-MB-231 and MDA-MB-468 cells and that the combination with miR-34c or miR-449a mimic strengthened the effect of the sulfonium compound through the modulation of β-catenin and Small Mother Against Decapentaplegic (SMAD) signaling pathways. Our results furnished the first evidence that AdoMet exerts its antitumor effects in TNBC cells through upregulating the expression of miR-34c and miR-449a.

Long non-coding RNA SNHG8 enhances triple-negative breast cancer cell proliferation and migration by regulating the miR-335-5p/PYGO2 axis

Biology Direct ◽

10.1186/s13062-021-00295-6 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Jintao Qian ◽

Xinhan Lei ◽

Yue Sun ◽

Lu Zheng ◽

Jia Li ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Triple Negative ◽

Luciferase Reporter ◽

Western Blot Assay ◽

Cell Proliferation And Migration ◽

Tnbc Cell ◽

And Migration ◽

Proliferation And Migration

Abstract Background Growing evidence has demonstrated that long non-coding RNAs (lncRNAs) can function as modulators in the development of triple-negative breast cancer (TNBC). However, the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in TNBC remains unclear. Therefore, our study aimed at investigating the role of SNHG8 in the proliferation and migration of TNBC cells. Methods SNHG8 expression was evaluated using RT-qPCR assay. Cell proliferation and migration were assessed by EdU, colony formation and Transwell assays. The levels of proteins related to EMT process were examined by western blot assay. The interaction among SNHG8, miR-335-5p and pygopus family PHD finger 2 (PYGO2) was detected by RIP assay, RNA pull down assay and luciferase reporter assay. Results SNHG8 expression was significantly up-regulated in TNBC cells. SNHG8 silencing obviously inhibited TNBC cell proliferation, migration and EMT process. Moreover, SNHG8 acted as a sponge to sequester miR-335-5p in TNBC cells. Besides, PYGO2 was proven as a target gene of miR-335-5p, and SNHG8 promoted TNBC cell proliferation, migration and EMT process through regulating miR-335-5p and PYGO2. Conclusions Totally, our study indicated that SNHG8 promoted TNBC cell proliferation and migration by regulating the miR-335-5p/PYGO2 axis.

E2F1 transcriptionally regulates CCNA2 expression to promote triple negative breast cancer tumorigenicity

Cancer Biomarkers ◽

10.3233/cbm-210149 ◽

2021 ◽

pp. 1-14

Author(s):

Yongbin Lu ◽

Fei Su ◽

Hui Yang ◽

Yi Xiao ◽

Xiaobin Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Breast Cancer Subtype ◽

Tumor Development ◽

Luciferase Reporter ◽

Invasion And Migration ◽

E2f Transcription Factor ◽

Highly Correlated ◽

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly malignant breast cancer subtype with a poor prognosis. The cell cycle regulator cyclin A2 (CCNA2) plays a role in tumor development. Herein, we explored the role of CCNA2 in TNBC. METHODS: We analyzed CCNA2 expression in 15 pairs of TNBC and adjacent tissues and assessed the relationship between CCNA2 expression using the tissue microarray cohort. Furthermore, we used two TNBC cohort datasets to analyze the correlation between CCNA2 and E2F transcription factor 1 (E2F1) and a luciferase reporter to explore their association. Through rescue experiments, we analyzed the effects of E2F1 knockdown on CCNA2 expression and cellular behavior. RESULTS: We found that CCNA2 expression in TNBC was significantly higher than that in adjacent tissues with similar observations in MDA-MB-231 and MDA-MB-468 cells. E2F1 was highly correlated with CCNA2 as observed through bioinformatics analysis (R= 0.80, P< 0.001) and through TNBC tissue verification analysis (R= 0.53, P< 0.001). We determined that E2F1 binds the +677 position within the CCNA2 promoter. Moreover, CCNA2 overexpression increased cell proliferation, invasion, and migration owing to E2F1 upregulation in TNBC. CONCLUSION: Our data indicate that E2F1 promotes TNBC proliferation and invasion by upregulating CCNA2 expression. E2F1 and CCNA2 are potential candidates that may be targeted for effective TNBC treatment.