Although many methods and new therapeutic drugs have been developed, the overall survival rate and long‐term survival rate of patients with gastric cancer (GC) are still not satisfactory. In this ...study, we investigated the effects of microRNA miR‐133a‐3p and transcription factor FOXP3 on proliferation and autophagy of GC cells and their interactions. Our results showed that knockdown of FOXP3 increased the proliferation and autophagy of GC cells. The relationship between FOXP3 and autophagy has not been reported previously. In addition, FOXP3 could directly bind the promoter region of TP53 and inhibit its expression. miR‐133a‐3p increased the proliferation and autophagy via decreasing the protein level of FOXP3 by targeting its 3′‐UTR. Our research provides new insights into the development of GC and provides new ideas and theoretical basis for the clinical treatment of GC and the development of new drug targets.
miR‐133a‐3p increased the proliferation and autophagy via decreasing the protein level of FOXP3 by targeting its 3′‐untranslated region. Our research provides new insights into the development of gastric cancer and provides new ideas and theoretical basis for the clinical treatment of gastric cancer and the development of new drug targets.
Epithelial-mesenchymal transition (EMT) plays an important role in breast cancer cell metastasis. Both (megakaryoblastic leukemia)/myocardin-like 1 (MKL-1) and Signal transducer and activator of ...transcription 3 (STAT3) have been implicated in the control of cellular metabolism, survival and growth. Our previous study has shown that cooperativity of MKL-1 and STAT3 promoted breast cancer cell migration. Herein, we demonstrate a requirement for MKL-1 and STAT3 in miRNA-mediated cellular EMT to affect breast cancer cell migration. Here we show that cooperativity of MKL-1 and STAT3 promoted the EMT of MCF-7 cells. Importantly, MKL-1 and STAT3 promoted the expression of Vimentin via its promoter CArG box. Interestingly, miR-93-5p inhibits the EMT of breast cancer cells through suppressing the expression of MKL-1 and STAT3 via targeted their 3’UTR. These results demonstrated a novel pathway through which miR-93-5p regulates MKL-1 and STAT3 to affect EMT controlling breast cancer cell migration.
•Cooperativity of MKL-1 and STAT3 promoted the EMT of MCF-7 cells.•Cooperativity of MKL-1 and STAT3 promoted the expression of Vimentin via its promoter CArG box.•MiR-93-5p inhibits the EMT of MCF-7 cells through suppressing MKL-1 and STAT3 via targeted their 3’UTR.
miR-5100 participates in the proliferation of lung cancer and pancreatic cancer cells, and participates in the differentiation of osteoblasts. However, the regulation of gastric cancer cells in ...gastric cancer cells remains unclear.
The blood of patients was collected to detect the expression level of miR-5100, and the apoptosis and autophagy levels of cells were detected using western blot, flow cytometry, and confocal. At the same time, in vitro tumor formation experiments in nude mice were used to verify the results of in vitro experiments.
The expression of miR-5100 is related to the prognosis of gastric cancer, miR-5100 can enhance the apoptosis level of gastric cancer cells and inhibit the occurrence of autophagy by targeting CAAP1. MKL1 can inhibit the apoptosis of gastric cancer cells and promote the occurrence of autophagy by targeting CAAP1. At the same time, MKL1 can also increase the expression of miR-5100.
Our research reveals the mechanism by which the MKL1/miR-5100/CAAP1 loop regulates apoptosis and autophagy levels in gastric cancer cells, and miR-5100 is expected to become a new potential target for gastric cancer treatment.
High expression of estrogen receptor α (ERα) is associated with a poor prognosis that correlates closely with cellular proliferation in breast cancer. However, the exact molecular mechanism by which ...ERα controls breast cancer cell proliferation is not clear. Here we report that ERα regulates the cell cycle by suppressing p53/p21 and up‐regulating proliferating cell nuclear antigen (PCNA) and proliferation‐related Ki–67 antigen (Ki–67) to promote proliferation of MCF–7 cells. In addition, 17–β–estradiol (E2) enhances ERα‐induced proliferation of MCF–7 cells by stimulating expression of PCNA and Ki–67. Knockdown of ERα significantly affects PCNA/Ki–67 and p53/p21 expression. Furthermore, ERα inhibits the transcriptional activity of p53/p21 in an estrogen response element‐dependent manner. More importantly, we provide new evidence that ERα mediates proliferation of MCF–7 cells by up‐regulating miR–17 to silence the expression of p21. Thus, these data provide new insights into the underlying effect of ERα on breast cancer proliferation.
Model for how estrogen receptor α (ERα) regulates MCF‐7 cell proliferation by p53‐p21‐PCNA‐E2F1 pathway.
It is always big challenges for hyaluronic acid (HA) in transmembrane absorbing and efficient delivering to the skin. Pep‐1, as one of the cell‐penetrating peptides, has been documented to permeate ...various substances across cellular membranes without covalent binding. Here, a novel hyaluronic acid binding peptide (named HaBP) is designed, and then combined with Pep‐1 to enhance the cell‐penetrating efficiency of HA. The results of ELISA and immunofluorescence assay show that HaBP could bind with HA very well, and a combination of Pep‐1 and HaBP could efficiently improve the transmembrane ability of HA. Furthermore, HA gradually enters the dermis from the surface of the skin in mice when it is administrated with both HaBP and Pep‐1, while there are no obvious allergies or other adverse reactions during this process. This study finds a new method to promote the efficient transmembrane and transdermal absorption of HA, and throws some light on further research on the development of hyaluronic acid and its related cosmetics or drugs.
Pep‐1 combined with HaBP enhances the cell‐penetrating efficiency of hyaluronic acid (HA) at the cell level and Transwell‐based 3D skin model in vitro. And Pep‐1/HaBP has good biocompatibility. This study finds a new method to promote the efficient transmembrane and transdermal absorption of HA and throws some light on further research on the development of HA and its related cosmetics or drugs.
Hypericum attenuatum Choisy is a traditional Chinese herbal plant with multiple therapeutic effects. In this study, bioactivity‐guided fractionation of Hypericum attenuatum Choisy extracts afforded ...three major flavonoids (including astragalin, guaijaverin and quercetin), which possessed α‐Glucosidase inhibitory activity with IC50 values of 33.90±0.68 μM, 17.23±0.75 μM and 31.90±0.34 μM, respectively. Circular dichroism analysis revealed that all the three compounds could interact with α‐glucosidase by inducing conformational changes of the enzyme. Molecular docking results indicated that they could bind to the active site in α‐glucosidase, and the binding force was driven mainly by hydrogen bond. Additionally, isobolographic analysis of the interactions between two compounds showed that all the combinations presented a synergistic α‐glucosidase inhibitory effect at lower concentrations, and the combination between quercetin and guaijaverin or astragalin exhibited the best synergistic effect. This research might provide a theoretical basis for the application of Hypericum attenuatum Choisy in treating hyperglycemia.
Long non-coding RNAs (lncRNAs) have emerged as a new and crucial layer of gene regulation in recent years and regulate various biological processes such as carcinogenesis and metastasis. LncRNA ...HOTAIR, an oncogenic lncRNA, is involved in human tumorigenesis and dysregulated in cervical cancer. Megakaryoblastic leukemia 1 (MKL1), as a transcription coactivity factor, involved in cancer metastasis and cell differentiation. However, the precise mechanism of biological roles of HOTAIR and MKL1 in cancer cells remain unclear.
The expression levels of HOTAIR and MKL1 were measured by quantitative PCR (qPCR), immunoblotting, in situ hybridization (ISH) and immunohistochemistry (IHC). Wound-healing and transwell assays were used to examine the invasive abilities of HeLa cells. Luciferase reporter assays and CHIP were used to determine how MKL1 regulates HOTAIR. Tissue microarray and immunohistochemical staining were used to assess the correlation between HOTAIR and MKL1 in Cervical cancer tissues in vivo.
In this study, we have identified that MKL1 had a role in the induction of migration and invasion in cervical cancer cells. Moreover, the expression level of MKL1, as the targeting gene of miR206, was decreased after HOTAIR inhibition in HeLa cells. Agreement with it, Highly level of MKL1 correlation with HOTAIR is validated in cervical cancer tissues. Importantly, HOTAIR is observed to participate in the silencing of miR206 expression. Interestingly, HOTAIR inhibition could also accelerate the expression of MKL1 in cytoplasm. What is more, MKL1 can activate the transcription of HOTAIR through binding the CArG box in the promoter of HOTAIR.
These elucidates that the phenotypic effects of migration and invasion observed after HOTAIR inhibition, at least in part, through the regulation of MKL1 via inhibition of miR206 expression in HeLa cells. These data indicate the existence of a positive feedback loop between HOTAIR and MKL1. Together, these findings suggest that MKL1 is an important player in the functions of HOTAIR in the migration and invasion of cancer cells.
Cell division cycle-associated 5 (CDCA5) plays a critical role in the progression of various human cancers by regulating cell cycle-related proteins; however, the function of CDCA5 in breast cancer ...(BC) is poorly understood. The aim of the present study was to investigate the expression level of CDCA5 in BC and its effect on BC progression. CDCA5 was found to be highly expressed in patients with BC, as well as in BC cell lines. It was also found that a high CDCA5 expression in BC was significantly associated with a shorter survival rate. In addition, the expression level of CDCA5 was significantly increased in stem cells derived from suspension-cultured BC cells, as compared to adherent-cultured cells. CDCA5 knockdown in MCF7 and SKBR3 cells significantly reduced cell proliferation, migration and clone formation. At the same time, the stemness capacity of BC cells, determined by analyzing cancer stem cell marker expression and mammosphere formation, was also markedly diminished following the knockdown of CDCA5. In addition, in vivo experiments demonstrated that CDCA5 knockdown in MCF7 cells markedly reduced tumor growth. On the whole, the present study demonstrates that CDCA5 may be used as a prognostic biomarker and therapeutic target for BC.
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•H. attenuatum was first reported to exhibit hypoglycemic effect in T2DM mice.•PI3K/AKT pathway was mediated in hypoglycemic effect of H. attenuatum.•H. attenuatum Choisy extracts ...could modulate the intestinal microbial communities.•H. attenuatum enriched SCFAs-producing bacteria in intestine.
Hypericum attenuatum Choisy, as an edible medicinal plant, possesses multiple therapeutic effects. Type 2 diabetes is a metabolic disorder that has become a major threat to public health. The objective of this study was to investigate the hypoglycemic effect of Hypericum attenuatum Choisy extracts (HaC) on T2DM mice and modulatory effect of HaC on composition of intestinal microflora. T2DM mice were treated with HaC for 5 weeks. HaC could modulate fasting blood glucose, improve hepatic insulin sensitivity and promote hepatic glycogen storage by activating IRS1/PI3K/AKT pathway. Moreover, HaC regulated dysfunctional lipid metabolism and reduced inflammation in T2DM mice. Additionally, HaC treatment could modulate the compositions of gut microbiota in small intestine and colon with the altered abundances of Firmicutes, Bacteroidetes and Proteobacteria. Meanwhile, HaC treatment could augment short chain fatty acids contents. These results demonstrate that H. attenuatum Choisy may be a potential therapy for the treatment of T2DM.
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