ABSTRACT
BACKGROUND: While current basic studies indicate adipose-derived stem cells (ADSCs) can promote cell proliferation, clinical trials have shown no significant difference in breast cancer recurrence rates for patients with or without autologous fat grafting (AFG). In this study we attempted to explore the underlying mechanism for these contradictory results. METHODS: ADSCs and umbilical mesenchymal stem cells (UMSCs) were co-cultured with breast cancer cells (MCF-7 and MDA-MB-231), and the cell viability analyzed by CCK-8 cell proliferation assay, TUNEL assay and immunofluorescence assay. In addition, real-time quantitative polymerase chain reaction (RT-qPCR) experiments and Western blot analysis were used to detect the mRNA and protein expression of activating transcription factor 4 (ATF4) and its downstream gene (MCL1 & BCL2), respectively. RESULTS: Co-cultured ADSCs could promote cell proliferation and cell apoptosis, and up-regulate ATF4 expression both in MCF-7 and MDA-MB-231. While co-cultured UMSCs could only promote cell apoptosis in MCF-7. Interestingly, we found that when co-cultured ADSCs, the expression of MCL1 and BCL2 protein was decreased, even if their mRNA expression was up-regulated both in MCF-7 and MDA-MB-231. CONCLUSIONS: Co-cultured ADSCs can up-regulate ATF4 expression, then interfere with the translation process of MCL1 and BCL2 mRNA and induce cell apoptosis. These data provide insight into the safety characteristics of AFG.
ABSTRACT
BACKGROUND: Breast cancer is an aggressive disease with high morbidity and mortality rates among women globally. Tumor protein D52 (TPD52) is an oncogene in breast cancer; however, its physiological function remains elusive. This study set out to obtain a deeper understanding of the functions of TPD52 in the pathophysiology of breast cancer by exploring its effects on breast cancer cell proliferation and migration. METHODS: Bioinformatics analysis was performed to predict the bonding of TPD52 and nuclear paraspeckle assembly transcript 1 (NEAT1) with miR-218-5p. The bonding of TPD52 and NEAT1 with miR-218-5p were verified by luciferase reporter assays. The mRNA expression of TPD52, miR-218-5p or NEAT1 were tested by Rt-qPCR and the protein expression of TPD52 was tested by western blot. Colony formation and EdU assays were carried out to evaluate cell proliferation. Wound healing and Transwell assays were used to evaluate migration. RESULTS: In this study, TPD52 was upregulated in breast cancer cells, and silencing of TPD52 repressed the proliferation and migration of breast cancer cells in vitro and in vivo. Further, microRNA (miR)-218-5p reduced the expression level of TPD52, while overexpression of TPD52 attenuated the effects of miR-218-5p mimics on breast cancer cell proliferation and migration. Also, NEAT1 acted as a competitive endogenous sponge of miR-218-5p to downregulate free miR-218-5p levels. It was further observed that TPD52 overexpression recovered the inhibition of breast cancer cell growth and migration caused by NEAT1 downregulation. These results confirmed the functions of NEAT1 in breast cancer and supported the mechanism of the NEAT1/miR-218-5p/TPD52 axis. CONCLUSIONS: Our findings highlight the important role of the NEAT1/miR-218-5p/TPD52 axis in breast cancer cell proliferation and migration. This axis may be a potential therapeutic target for breast cancer.
ABSTRACT
To analyse genetic variability and population structure, 84 isolates of Echinococcus granulosus (Cestoda: Taeniidae) collected from various host species at different sites of the Tibetan plateau in China were sequenced for the whole mitochondrial nad1 (894 bp) and atp6 (513 bp) genes. The vast majority were classified as G1 genotype (n=82), and two samples from human patients in Sichuan province were identified as G3 genotype. Based on the concatenated sequences of nad1+atp6, 28 different haplotypes (NA1-NA28) were identified. A parsimonious network of the concatenated sequence haplotypes showed star-like features in the overall population, with NA1 as the major haplotype in the population networks. By AMOVA it was shown that variation of E. granulosus within the overall population was the main pattern of the total genetic variability. Neutrality indexes of the concatenated sequence (nad1+atp6) were computed by Tajima's D and Fu's Fs tests and showed high negative values for E. granulosus, indicating significant deviations from neutrality. FST and Nm values suggested that the populations were not genetically differentiated.
