Effect of STX5 on the metastasis of hepatocellular carcinoma and its mechanism

Objective To investigate the effect of STX5 on the metastasis of hepatocellular carcinoma (HCC) and its mechanism. Methods Clinical data were collected from 36 patients who were diagnosed with HCC in our hospital from January to December 2015, and the correlation between the expression level of STX5 in tumor tissue and the clinicopathological features of HCC patients was analyzed. Human hepatoma cells MHCC97H were divided into groups A and B and were transfected with negative control plasmid and STX5 overexpression plasmid, respectively. Human hepatoma cells Huh7 were divided into groups C and D and were transfected with negative control lentivirus and STX5 knockdown virus, respectively. Western blot was used to measure the protein expression level of STX5 in groups A, B, C, and D, wound healing was used to measure the migration ability of cells in groups A, B, C, and D, and Transwell assay was used to measure the migration ability of cells in groups A, B, C, and D. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were performed for the differentially expressed genes in groups A and B obtained by transcriptomic sequencing, and RT-qPCR was used to measure the levels of the most significantly differentially expressed genes in group A and B. MHCC97H cells were divided into groups E, F, G, and H and were transfected with negative control plasmid, STX5 overexpression plasmid, negative control plasmid+Sarilumab, and STX5 overexpression plasmid+Sarilumab, respectively. Scratch assay was used to measure the migration ability of cells in groups E, F, G, and H, and Transwell assay was used to measure the migration ability of cells in groups E, F, G, and H. Results The expression level of STX5 in tumor tissue was associated body mass index, presence or absence of hepatitis B virus infection, and the number of tumors (P<0.05). Western blot showed that group B had a significantly higher expression level of STX5 than group A, and group C had a significantly higher expression level of STX5 than group D (t=48.86,31.09,P<0.05). Transwell test and wound healing showed that compared with group A, group B had significantly higher ability of cell invasion and percentage of scratch healing, and compared with group D, group C had significantly higher ability of cell migration and percentage of scratch healing (t=7.95-31.09,P<0.05). The GO and KEGG enrichment analyses showed that the differentially expressed genes between groups A and B were mainly enriched in the functions and pathways associated with cell migration and inflammation, and RT-qPCR showed that group B had a significantly higher mRNA expression level of IL-6 than group A (t=23.69,P<0.05). Transwell assay and wound healing showed that group G had significantly lower ability of cell migration and percentage of scratch healing than group E, and group H had significantly lower ability of cell invasion and percentage of scratch healing than group F (t=2.94-24.39,P<0.05). Conclusion STX5 can promote the migration and metastasis of HCC cells by upregulating the mRNA expression level of IL-6

TGF-β Signaling in Progression of Oral Cancer

Oral cancer is a common malignancy worldwide, accounting for 1.9% to 3.5% of all malignant tumors. Transforming growth factor β (TGF-β), as one of the most important cytokines, is found to play complex and crucial roles in oral cancers. It may act in a pro-tumorigenic and tumor-suppressive manner; activities of the former include cell cycle progression inhibition, tumor microenvironment preparation, apoptosis promotion, stimulation of cancer cell invasion and metastasis, and suppression of immune surveillance. However, the triggering mechanisms of these distinct actions remain unclear. This review summarizes the molecular mechanisms of TGF-β signal transduction, focusing on oral squamous cell and salivary adenoid systemic carcinomas as well as keratocystic odontogenic tumors. Both the supporting and contrary evidence of the roles of TGF-β is discussed. Importantly, the TGF-β pathway has been the target of new drugs developed in the past decade, some having demonstrated promising therapeutic effects in clinical trials. Therefore, the achievements of TGF-β pathway-based therapeutics and their challenges are also assessed. The summarization and discussion of the updated knowledge of TGF-β signaling pathways will provide insight into the design of new strategies for oral cancer treatment, leading to an improvement in oral cancer outcomes

Oral microbiomes: more and more importance in oral cavity and whole body

ABSTRACT Microbes appear in every corner of human life, and microbes affect every aspect of human life. The human oral cavity contains a number of different habitats. Synergy and interaction of variable oral microorganisms help human body against invasion of undesirable stimulation outside. However, imbalance of microbial flora contributes to oral diseases and systemic diseases. Oral microbiomes play an important role in the human microbial community and human health. The use of recently developed molecular methods has greatly expanded our knowledge of the composition and function of the oral microbiome in health and disease. Studies in oral microbiomes and their interactions with microbiomes in variable body sites and variable health condition are critical in our cognition of our body and how to make effect on human health improvement

Midpalatal Suture: Single-Cell RNA-Seq Reveals Intramembrane Ossification and Piezo2 Chondrogenic Mesenchymal Cell Involvement

The midpalatal suture is mainly responsible for the growth and development of the maxillary and resistance to rapid maxillary expansion (RME). It is essential for clinical researchers to explore the intramembrane ossification and to elucidate the underlying mechanism of the maturation and ossification process of the midpalatal suture to help identify the optimum time and force of RME. However, mechanistic studies associated with the midpalatal suture are rare. The aim of this present study is to create an intramembrane osteogenesis model for the midpalatal suture region of mice. Interestingly, we discovered a type of chondrogenic mesenchymal cell expressing Piezo2, which might be related to the detection of mechanical and external stimuli. This result provides a potential molecular and cellular mechanism that explains why the midpalatal suture is not closed until adulthood. We depict a landscape of mesenchymal cells that might play an important role in the intramembrane osteogenesis of the midpalatal suture and provide new perspectives on midpalate suture maturation and ossification, which might lead to further possibilities for clinical operations

Icariin-Curcumol promotes docetaxel sensitivity in prostate cancer through modulation of the PI3K-Akt signaling pathway and the Warburg effect

Abstract Background Docetaxel (DTX) resistance reduces therapeutic efficacy in prostate cancer (PCa). Accumulating reports support the role of phytochemicals in the reversal of DTX resistance. This study aimed to determine whether Epimedium brevicornu and Curcuma zedoaria extracts (ECe), specially icariin-curcumol, attenuates DTX resistance and explore their potential mechanisms. Methods Regulatory pathways were predicted between ECe active ingredients and PCa using network pharmacology. DTX-resistant cell LNCaP/R were established based on DTX-sensitive LNCaP, and xenograft models were further established. Active ingredients in ECe by HLPC-MS were identified. The binding of icariin and curcumol to the target was analyzed by molecular docking. Biochemical experiments were applied to determine the possible mechanisms by which Icariin-Curcumol regulates DTX sensitivity. Results Akt1 and the PI3K-Akt signaling pathway were predicted as the primary functional target between drug and PCa. ECe and DTX inhibited xenograft tumor growth, inflammation, cell viability and promoted apoptosis. Icariin and curcumol were detected in ECe, and icariin and curcumol docked with Akt1. ECe, Icariin-Curcumol and DTX downregulated AR, PSA, PI3K, Akt1, mTOR, and HIF-1ɑ. Moreover, ECe, Icariin-Curcumol and DTX increased glucose and PDH, decreased lactic acid, ATP and LDH, and downregulated c-Myc, hnRNPs, VEGF, PFK1, and PKM2. Notably, the anti-PCa effect of DTX was attenuated compared to ECe or Icariin-Curcumol in the LNCaP/R model. The combined effect of Icariin-Curcumol and DTX was superior to that of DTX. Conclusion Our data support that Icariin-Curcumol reverses DTX resistance by inhibiting the PI3K-Akt signaling and the Warburg effect, providing new ideas for improving therapeutic measures for PCa

A DAAM1 3′-UTR SNP mutation regulates breast cancer metastasis through affecting miR-208a-5p-DAAM1-RhoA axis

Abstract Background Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a member of microfilament-related formins and mediates cell motility in breast cancer (BrCa). However, the genetic mutation status of DAAM1 mRNA and its correlation with pathological characteristics are still unclearly. Methods A patient cohort and BrCa cells were recruited to demonstrate the role of functional SNP in microRNA-208a-5p binding site of DAAM1 3′-UTR and underlying mechanism in BrCa metastasis. Results The expression and activation of DAAM1 increased markedly in lymphnode metastatic tissues. A genetic variant (rs79036859 A/G) was validated in the miR-208a-5p binding site of DAAM1 3′-UTR. The G genotype (AG/GG) was a risk genotype for the metastasis of BrCa by reducing binding affinity of miR-208a-5p for the DAAM1 3′-UTR. Furthermore, the miR-208a-5p expression level was significantly suppressed in lymphnode metastatic tissues compared with that in non-lymphnode metastatic tissues. Overexpression of miR-208a-5p inhibited DAAM1/RhoA signaling pathway, thereby leading to the decrease of the migratory ability. Conclusion Overall, the rs79036859 G variant of DAAM1 3′-UTR was identified as a relevant role in BrCa metastasis via the diversity of miR-208a-5p binding affinity

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer

Abstract Background Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. Methods A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. Results After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3+CD8+IFN-γ, CD3+CD8+Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. Conclusions ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa