MicroRNA-367 Inhibits Breast Cancer and Promotes Apoptosis by Targeting AT-Rich Interactive Domain-Containing Protein 1B

Introduction: Breast cancer (BC) developed in the glandular epithelial tissue of breast. microRNA (miR)-367 is an important player in cancer progression, but has never been studied in BC. This experiment tries to probe the mechanism of miR-367 in BC treatment with downstream target gene. Materials and Methods: Human BC cell lines and healthy breast epithelium cells were applied in this study. After the transfection of miR-367 inhibitor or mimic into BC cells, functional assays were conducted to measure cell growth. Afterwards, flow cytometry was employed in apoptosis verification. Then, target relation between miR-367 and ARID1B was certified. Furthermore, ARID1B level was also measured. Results: miR-367 was underexpressed in human BC cells (p < 0.05). Besides, overexpressed miR-367 inhibited BC cell proliferation and encouraged apoptosis, while underexpressed miR-367 led to an opposite outcome (p < 0.05). This experiment then implied that miR-367 dramatically suppressed the activity of cell transfected with ARID1B-wild type. miR-367 overexpression quenched ARID1B level in BC cells; while silencing miR-367 upregulated ARID1B expression (p < 0.05). Conclusion: Our experiment discovered that miR-367 quenched BC cell growth and promoted apoptosis by targeting ARID1B. This investigation may provide novel insights in BC treatment.

Up-Regulation of miR-1925 by Bone Marrow Mesenchymal Stem Cell (BMSC) Inhibits the Growth of Liver Cancer by Promoting the Anti-Tumor Activity of Natural Killer (NK) Cells

Hepatocellular carcinoma (HCC) seriously threatens human health and life quality. Natural killer (NK) cells play important roles in liver immune function. Bone marrow mesenchymal stem cell (BMSC) exosomes (Exo) participate in tissue damage. This study explored BMSC-Exo’s effect on NK cells’ anti-tumor activity. NK cells were isolated from the livers of mice with liver cancer. NK cells with or without BMSC-Exo treatment were co-cultured with liver cancer cells to assess cell proliferation. Administration of BMSC-Exo into mice with liver cancer significantly suppressed liver cancer cell growth. In addition, BMSC-Exo treatment significantly improved NK cells’ anti-tumor effect whic was related to BMSC-Exo-induced up-regulation of miR-1925. Implantation of BMSC-Exo into mice with liver cancer at different time periods can significantly suppress liver cancer cell growth. At the same time, BMSC-Exo implantation inhibited the expression of cell proliferation marker protein(Ki67). In vitro study found that BMSC-Exo treatment significantly increased miR-1925 level and the toxicity of NK cells to HCC cells. In addition, miR-1925 overexpression in NK cells significantly increased NK cells’ anti-tumor activity. In conclusion, this study proved that up-regulation of miR-1925 by BMSC can inhibit the growth of liver cancer by promoting the anti-tumor activity of NK cells.

Cold Atmospheric Plasma Attenuates Breast Cancer Cell Growth Through Regulation of Cell Microenvironment Effectors

Breast cancer exists in multiple subtypes some of which still lack a targeted and effective therapy. Cold atmospheric plasma (CAP) has been proposed as an emerging anti-cancer treatment modality. In this study, we investigated the effects of direct and indirect CAP treatment driven by the advantageous nanosecond pulsed discharge on breast cancer cells of different malignant phenotypes and estrogen receptor (ER) status, a major factor in the prognosis and therapeutic management of breast cancer. The main CAP reactive species in liquid (i.e. H2O2, NO2−/NO3−) and gas phase were determined as a function of plasma operational parameters (i.e. treatment time, pulse voltage and frequency), while pre-treatment with the ROS scavenger NAC revealed the impact of ROS in the treatment. CAP treatment induced intense phenotypic changes and apoptosis in both ER+ and ER- cells, which is associated with the mitochondrial pathway as evidenced by the increased Bax/Bcl-2 ratio and cleavage of PARP-1. Interestingly, CAP significantly reduced CD44 protein expression (a major cancer stem cell marker and matrix receptor), while differentially affected the expression of proteases and inflammatory mediators. Collectively, the findings of the present study suggest that CAP suppresses breast cancer cell growth and regulates several effectors of the tumor microenvironment and thus it could represent an efficient therapeutic approach for distinct breast cancer subtypes.

Prostate cancer cell proliferation is influenced by LDL-cholesterol availability and cholesteryl ester turnover

Background Prostate cancer growth is driven by androgen receptor signaling, and advanced disease is initially treatable by depleting circulating androgens. However, prostate cancer cells inevitably adapt, resulting in disease relapse with incurable castrate-resistant prostate cancer. Androgen deprivation therapy has many side effects, including hypercholesterolemia, and more aggressive and castrate-resistant prostate cancers typically feature cellular accumulation of cholesterol stored in the form of cholesteryl esters. As cholesterol is a key substrate for de novo steroidogenesis in prostate cells, this study hypothesized that castrate-resistant/advanced prostate cancer cell growth is influenced by the availability of extracellular, low-density lipoprotein (LDL)-derived, cholesterol, which is coupled to intracellular cholesteryl ester homeostasis. Methods C4-2B and PC3 prostate cancer cells were cultured in media supplemented with fetal calf serum (FCS), charcoal-stripped FCS (CS-FCS), lipoprotein-deficient FCS (LPDS), or charcoal-stripped LPDS (CS-LPDS) and analyzed by a variety of biochemical techniques. Cell viability and proliferation were measured by MTT assay and Incucyte, respectively. Results Reducing lipoprotein availability led to a reduction in cholesteryl ester levels and cell growth in C4-2B and PC3 cells, with concomitant reductions in PI3K/mTOR and p38MAPK signaling. This reduced growth in LPDS-containing media was fully recovered by supplementation of exogenous low-density lipoprotein (LDL), but LDL only partially rescued growth of cells cultured with CS-LPDS. This growth pattern was not associated with changes in androgen receptor signaling but rather increased p38MAPK and MEK1/ERK/MSK1 activation. The ability of LDL supplementation to rescue cell growth required cholesterol esterification as well as cholesteryl ester hydrolysis activity. Further, growth of cells cultured in low androgen levels (CS-FCS) was suppressed when cholesteryl ester hydrolysis was inhibited. Conclusions Overall, these studies demonstrate that androgen-independent prostate cancer cell growth can be influenced by extracellular lipid levels and LDL-cholesterol availability and that uptake of extracellular cholesterol, through endocytosis of LDL-derived cholesterol and subsequent delivery and storage in the lipid droplet as cholesteryl esters, is required to support prostate cancer cell growth. This provides new insights into the relationship between extracellular cholesterol, intracellular cholesterol metabolism, and prostate cancer cell growth and the potential mechanisms linking hypercholesterolemia and more aggressive prostate cancer.

Promoting Cell Growth And Poly-Y-Glutamic Acid Production By Boosting The Synthesis of Alanine And D-Alanyl-D-Alanine In Bacillus Licheniformis

Objective: The production of some bio-chemicals affected by the cell growth. This study aimed at promoting the cell growth by overexpressing the synthesis of peptidoglycans tetrapeptide tail components to improve poly-γ-glutamic acid (γ-PGA) production. Results: L-alanine, D-alanine and D-alanyl-D-alanine are primary precursors for the synthesis of peptidoglycans. The addition of L-alanine and D-alanine significantly increased both the cell growth and production of γ-PGA. Then, several genes encoding key enzymes for L/D-alanine and D-alanyl-D-alanine biosynthesis were overexpressed respectively, including ald (encoding alanine dehydrogenase), dal (encoding alanine racemase) and ddl (encoding D-alanine ligase). The results showed that the overexpression of genes ald , dal and ddl increased the production of γ-PGA by 19.72%, 15.91% and 60.90%, and increased the microbial biomass by 15.58%, 18.34% and 49.85%, respectively. Moreover, we demonstrated that the overexpression of genes ald , dal and ddl increased γ-PGA production mainly by enhancing cell growth rather than providing more precursors. Conclusions: This work illustrated the importance of the L/D-alanine and D-alanyl-D-alanine synthesis to the cell growth and the high yield of γ-PGA, and provided an effective strategy for producing γ-PGA .

Metabolomics-Driven Elucidation of Interactions between Saccharomyces cerevisiae and Lactobacillus panis from Chinese Baijiu Fermentation Microbiome

Saccharomyces cerevisiae and Lactobacillus panis are ethanol and lactic acid producers in Maotai-flavor Baijiu fermentation. Understanding their interaction is important to regulate the microbiome composition during fermentation and biosynthesis of ethanol and lactic acid. This study is the first to analyze the interaction between S. cerevisiae and L. panis at different growth phases during co-cultivation. Results showed that the different growth phases of S. cerevisiae modulated L. panis growth. Metabolomics analysis showed that amino acids and nucleoside secreted by S. cerevisiae promote L. panis growth, while ethanol inhibited L. panis growth. Furthermore, S. cerevisiae modulated L. panis cell growth under varying sugar concentrations. Simulated solid-state fermentation demonstrated that regulating the sugar concentration or the ratio of S. cerevisiae to L. panis could inhibit L. panis cell growth and reduce lactic acid accumulation. This study provided an understanding on Maotai-flavor Baijiu microbiome, which might be useful for metabolite regulation.

HIPK3 Inhibition by Exosomal hsa-miR-101-3p Is Related to Metabolic Reprogramming in Colorectal Cancer

BackgroundExosomes are extracellular vesicles secreted by most cells to deliver functional cargoes to recipient cells. MicroRNAs (miRNAs) constitute a significant part of exosomal contents. The ease of diffusion of exosomes renders them speedy and highly efficient vehicles to deliver functional molecules. Cancer cells secrete more exosomes than normal cells. Reports have showed that exosomal miRNAs of cancer cells facilitate cancer progression. Yet the complexity of cancer dictates that many more functional exosomal miRNAs remain to be discovered.MethodsIn this study, we analyzed miRNA expression profiles of tissue and plasma exosome samples collected from 10 colorectal cancer (CRC) patients and 10 healthy individuals. We focused on hsa-miR-101-3p (101-3p), a profoundly up-regulated miRNA enriched in plasma exosomes of patients bearing CRC. We performed target analysis of 101-3p and pursued functional studies of this microRNA in two colorectal cancer cell lines, namely HCT116 and SW480.ResultsOur results indicated that inhibiting 101-3p slowed cell growth and retarded cell migration in vivo in two colorectal cancer cell lines. Target analysis showed that Homeodomain-interacting protein kinase (HIPK3) is a target of miR-101-3p. HCT116 and SW480 cells stably overexpressing HIPK3 showed increased level of phosphorylated FADD, as well as retarded cell growth, migration, and increased sensitivity to 5-FU. In-depth analysis revealed increased mitochondrial membrane potential upon HIPK3 overexpression along with increased production of reactive oxygen species, number of mitochondria, and expression of respiratory complexes. Measurements of glycolytic parameters and enzymes revealed decreased level of glycolysis upon HIPK3 overexpression in these two cell lines. Xenograft model further confirmed a profoundly improved potency of the synergistic treatment combining both 5-FU and 101-3p inhibitor compared to 5-FU alone.ConclusionThis study unraveled an oncogenic nature of the exosomal 101-3p and suggested a relationship between the 101-3p-HIPK3 axis and metabolic homeostasis in colorectal cancer. Expression level of 101-3p is positively correlated with glycolytic capacity in CRC and therefore 101-3p itself is an oncomiR. Combining 101-3p inhibitor with chemotherapeutic agents is an effective strategy against CRC.