LncRNA AFAP1-AS1 mediates breast cancer cell proliferation and migration through the miR-21/PTEN axis.

LncRNAs play various effects, mostly by sponging with miRNAs. Based on public databases integrating bioinformatics analyses and further validation in breast cancer (BC) tissue and cell lines, the effect of lncRNA AFAP1-AS1 on breast cancer cell proliferation and migration was verified. It might work via the miR-21/PTEN axis. The expression of AFAP1-AS1, which was significantly upregulated in BC tissues and cell lines, was correlated with old age and lymph node metastasis of patients with BC. Knockdown of AFAP1-AS1 inhibited the proliferation and migration of BC cells in vitro and in vivo. And downregulated miR-21 expression and upregulated PTEN expression additionally. Mechanistically, the knockdown of lncRNA AFAP1-AS1 upregulated PTEN expression and consequently attenuated miR-21-mediated enhanced BC cell proliferation and migration. LncRNA AFAP1-AS1 is a potential prognostic biomarker for BC patients.

Cardiovascular risk factors and breast cancer incidence in a large middle-aged cohort study.

BACKGROUND: Several studies have demonstrated that cardiovascular risk factors play a role in the etiology of breast cancer. However, the combined effect of cardiovascular risk factors on the risk of breast cancer is still uncertain. METHODS: Data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort of middle-aged women, were used to investigate the association of individual and combined cardiovascular risk factors with breast cancer. Cox proportional hazards models were applied to calculate the hazard ratio (HR) and 95% confidence intervals (CI). RESULTS: A total of 7501 women were included. During a mean follow-up of 19.7 years, 576 women were diagnosed with breast cancer. White women and premenopausal status were independently associated with increased risk of breast cancer. Of the individual cardiovascular risk factors, only obesity was independently associated with an increased risk of breast cancer (HR 1.29, 95% CI 1.04-1.61). Compared with women without cardiovascular risk factors, women having three or greater, but not those with fewer than three cardiovascular risk factors, had a significantly higher risk of developing breast cancer (HR 1.27, 95% CI 1.06-1.53). Subgroup analyses indicated that women with three or greater cardiovascular risk factors had higher risk of breast cancer among postmenopausal Black women, but not among premenopausal Black and White women. CONCLUSIONS: Combinations of cardiovascular risk factors are associated with increased risk of breast cancer in middle-aged women, especially in postmenopausal Black women. Joint interventions to modify cardiovascular risk factors could be used to prevent breast cancer in these higher-risk individuals.

Integrated analyses of long noncoding RNAs and mRNAs in the progression of breast cancer.

OBJECTIVE: The objective was to explore the expression and potential functions of long noncoding RNA (lncRNA) and mRNAs in human breast cancer (BC). METHODS: Differentially expressed lncRNAs and mRNAs were identified and annotated in BC tissues by using the Agilent human lncRNA assay (Agilent Technologies, Santa Clara, CA, USA) and RNA sequencing. After identification of lncRNAs and mRNAs through quantitative reverse transcription polymerase chain reaction, we conducted a series of functional experiments to confirm the effects of knockdown of one lncRNA, TCONS_00029809, on the progression of BC. RESULTS: We discovered 238 lncRNAs and 200 mRNAs that were differentially expressed in BC tissues and para-carcinoma tissue. We showed that differentially expressed mRNAs were related to biological adhesion and biological regulation and mainly enriched in cytokine-cytokine receptor interaction, metabolic pathways, and PI3K-Akt signaling pathway. We created a protein-protein interaction network to analyze the proteins enriched in these pathways. We demonstrated that silencing of TCONS_00029809 remarkably inhibited proliferation, invasion, and migration of BC cells, and accelerated their apoptosis. CONCLUSIONS: We identified a large number of differentially expressed lncRNAs and mRNAs, which provide data useful in understanding BC carcinogenesis. The lncRNA TCONS_00029809 may be involved in the development of BC.

MiR-491-5p, as a Tumor Suppressor, Prevents Migration and Invasion of Breast Cancer by Targeting ZNF-703 to Regulate AKT/mTOR Pathway.

BACKGROUND: Large amounts of microRNAs (miRNAs) have been reported to be aberrantly expressed in malignant cancers. MiR-491-5p makes a significant contribution to the inhibition of multiple cancer processes. However, the specific mechanism and function of miR-491-5p and in breast cancer (BC) is still not fully elucidated. METHODS: MiR-491-5p and ZNF-703 expressions or gene transfection effects were identified by RT-qPCR or Western blot in BC tissues or cells. And ZNF-703 expression was monitored through immunohistochemistry method. Cellular function was also confirmed using Transwell assay. Besides, AKT/mTOR pathway-related proteins were analyzed using Western blotting analysis. Moreover, the interplay between miR-491-5p and ZNF-703 was verified through dual-luciferase reporter assay. RESULTS: miR-491-5p was lowly expressed, ZNF-703 was highly expressed in BC, and miR-491-5p with low expression and ZNF-703 with high expression were associated with poor prognosis of BC patients. Results of cellular function revealed that overexpression of miR-491-5p markedly suppressed BC cell migration and invasion, and knockdown of miR-491-5p had the opposite effect. Besides, mechanism research disclosed that miR-491-5p directly could bind to ZNF-703 and downregulate ZNF-703. Moreover, we proved that ZNF-703 could prominently reverse the influences of miR-491-5p on the migration and invasion of BC cells. More importantly, the data revealed that miR-491-5p repressed AKT/mTOR pathway by ZNF-703 in BC cells. CONCLUSION: MiR-491-5p prominently suppresses the metastasis of BC cells through ZNF-703 to regulate AKT/mTOR pathway, indicating that miR-491-5p and ZNF-703 might be served as the potential therapeutic targets for BC.