Accumulating evidence suggests neuronal apoptosis has the potential to lead to more harmful effects in the pathological processes following traumatic brain injury (TBI). Previous studies have established that milk fat globule-EGF factor-8 (MFG-E8) provides neuroprotection through modulation of inflammation, oxidative stress, and especially apoptosis in cerebral ischemia and neurodegenerative disease. However, the effects of MFG-E8 on neuronal apoptosis in TBI have not yet been investigated. Therefore, we explored the role of MFG-E8 on anti-apoptosis and its potential mechanism following TBI. In the first set of experiments, adult male Sprague-Dawley (SD) rats were randomly divided into Sham and TBI groups that were each further divided into five groups representing different time points (6 h, 24 h, 72 h, and 7 days) (n = 9 each). Western blotting, quantitative real-time PCR, and immunofluorescence staining were performed to identify the expression and cellular localization of MFG-E8. In the second set of experiments, four groups were randomly assigned: Sham group, TBI + Vehicle group, and TBI + rhMFG-E8 (1 and 3 µg) (n = 15). Recombinant human MFGE8 (rhMFG-E8) was administrated as two concentrations through intracerebroventricular (i.c.v.) injection at 1 h after TBI induction. Brain water content, neurological severity score, western blotting, and immunofluorescence staining were measured at 24 and 72 h following TBI. In the final set of experiments, MFG-E8 siRNA (500 pmol/3 µl), integrin β3 siRNA (500 pmol/3 µl), and PI3K inhibitor LY294002 (5 and 20 µM) were injected i.c.v. and thereafter rats exposed to TBI. Western blotting, immunofluorescence staining, brain water content, neurological severity score, and Fluoro-Jade C (FJC) staining were used to investigate the effect of the integrin-β3/FAK/PI3K/AKT signaling pathway on MFG-E8-mediated anti-apoptosis after TBI. The expression of MFG-E8 was mainly located in microglial cells and increased to peak at 24 h after TBI. Treatment with rhMFG-E8 (3 µg) markedly decreased brain water content, improved neurological deficits, and reduced neuronal apoptosis at 24 and 72 h after TBI. rhMFG-E8 significantly enhanced the expression of integrin-β3/FAK/PI3K/AKT pathway-related components. Administration of integrin-β3 siRNA and LY294002 (5 and 20 µM) abolished the effect of rhMFG-E8 on anti-apoptosis and neuroprotection after TBI. This study demonstrated for the first time that rhMFG-E8 inhibits neuronal apoptosis and offers neuroprotection. This is suggested to occur through the modulation of the integrin-β3/FAK/PI3K/AKT signaling pathway, highlighting rhMFG-E8 as a potentially promising therapeutic strategy for TBI patients.

Human ribosomes have long been thought to be uniform factories with little regulatory function. Accumulating evidence emphasizes the heterogeneity of ribosomal protein (RP) expression in specific cellular functions and development. However, a systematic understanding of functional relevance of RPs is lacking. Here, we surveyed translational and transcriptional changes after individual knockdown of 75 RPs, 44 from the large subunit (60S) and 31 from the small subunit (40S), by Ribo-seq and RNA-seq analyses. Deficiency of individual RPs altered specific subsets of genes transcriptionally and translationally. RP genes were under cotranslational regulation upon ribosomal stress, and deficiency of the 60S RPs and the 40S RPs had opposite effects. RP deficiency altered the expression of genes related to eight major functional classes, including the cell cycle, cellular metabolism, signal transduction and development. 60S RP deficiency led to greater inhibitory effects on cell growth than did 40S RP deficiency, through P53 signaling. Particularly, we showed that eS8/RPS8 deficiency stimulated apoptosis while eL13/RPL13 or eL18/RPL18 deficiency promoted senescence. We also validated the phenotypic impacts of uL5/RPL11 and eL15/RPL15 deficiency on retina development and angiogenesis, respectively. Overall, our study provides a valuable resource for and novel insights into ribosome regulation in cellular activities, development and diseases.

It has been demonstrated that hydrogen sulfide plays a vital role in physiological and pathological processes such as regulating inflammation, oxidative stress, and vessel relaxation. The aim of the study was to explore the effect of hydrogen sulfide on angiogenesis in the ischemic adductor muscles of type 2 diabetic db/db mice and ischemic diabetic wound healing.

Non-small cell lung cancer (NSCLC) is a major pathological type of lung cancer. However, its pathogenesis remains largely unclear. MRPL35 is a regulatory subunit of the mitoribosome, which can regulate the assembly of cytochrome c oxidases and plays an important role in the occurrence of NSCLC.

The purpose of this study was to investigate whether aerobic exercise training inhibits atherosclerosis via the reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) expression in balloon-induced common carotid arteries of a high-fat-diet rats. Male SD (Sprague Dawley) rats fed an eight-weeks high-fat diet were randomly divided into three groups; these were the sham-operated control (SC), the balloon-induced control (BIC) and the balloon-induced exercise (BIE). The aerobic exercise training groups were performed on a treadmill. The major findings were as follows: first, body weight gain was significantly decreased by aerobic exercise training compared to the BIC without change of energy intake. Second, neointimal formation was significantly inhibited by aerobic exercise training in the balloon-induced common carotid arteries of high-fat-diet rats compared to the BIC. Third, low-density lipoprotein (LDL) receptor (LDLr) expression was significantly increased by aerobic exercise training in the livers of the high-fat diet group compared to the BIC, but not the proprotein convertase subtilisin/kexin type 9 (PCSK9) expression. Fourth, aerobic exercise training significantly decreased the expression of PCSK9, the lectin-like oxidized LDL receptor-1 (LOX-1), and vascular cell adhesion molecule-1 (VCAM-1) in balloon-induced common carotid arteries of high-fat-diet rats compared to the BIC. In conclusion, our results suggest that aerobic exercise training increases LDLr in the liver and inhibits neointimal formation via the reduction of PCSK9 and LOX-1 in balloon-induced common carotid arteries of high-fat-diet-induced rats.

Lamin A/C (LMNA) gene mutations are a known cause of familial dilated cardiomyopathy, but the precise mechanisms triggering disease progression remain unknown. We hypothesize that analysis of differentially expressed genes (DEGs) throughout the course of Lmna knockout (Lmna-/-)-induced cardiomyopathy may reveal novel Lmna-mediated alterations of signaling pathways leading to dilated cardiomyopathy. Although Lmna was the only DEG down-regulated at 1 week of age, we identified 730 and 1004 DEGs in Lmna-/- mice at 2 weeks and 1 month of age, respectively. At 2 weeks, Lmna-/- mice demonstrated both down- and up-regulation of the key genes involving cell cycle control, mitochondrial dysfunction, and oxidative phosphorylation, as well as down-regulated genes governing DNA damage repair and up-regulated genes involved in oxidative stress response, cell survival, and cardiac hypertrophy. At 1 month, the down-regulated genes included those involved in oxidative phosphorylation, mitochondrial dysfunction, nutrient metabolism, cardiac β-adrenergic signaling, action potential generation, and cell survival. We also found 96 overlapping DEGs at both ages involved in oxidative phosphorylation, mitochondrial function, and calcium signaling. Impaired oxidative phosphorylation was observed at early disease stage, even before the appearance of disease phenotypes, and worsened with disease progression, suggesting its importance in the pathogenesis and progression of LMNA cardiomyopathy. Reduction of oxidative stress might therefore prevent or delay the development from Lmna mutation to LMNA cardiomyopathy.

Homeobox protein Nxk-2.5 (Nkx2.5) is a homeobox transcription factor that promotes chamber-like myocardial gene expression. Data from a previous genome-wide association study suggested that Nkx2.5 may be associated with the genetic variation that underlies atrial fibrillation (AF). Nkx2.5 loss of function has been demonstrated to be associated with an increasing susceptibility of familial AF. Therefore, the aim of the present study was to investigate the effect of Nkx2.5 loss of function on electrophysiological substrates in HL-1 cells. To the best of our knowledge, the results demonstrated for the first time that Nkx2.5 expression was significantly decreased in a rat model exhibiting AF. The effect of silencing Nkx2.5 was assessed following transfection with adenoviral vectors with specific NKX2.5-shRNA. The effect of Nkx2.5 silencing on potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), gap junction alpha-5 protein (Cx40), calcium handling proteins and protein Wnt-11 (Wnt11) expression levels was also assessed in HL-1 cells. The results revealed that Nkx2.5 silencing increased HCN4 expression, decreased Cx40 expression and disrupted the expression of calcium handling proteins. Additionally, Wnt11 signal protein expression was decreased following Nkx2.5 silencing. The results of the present study demonstrated that Nkx2.5 served as a transcriptional regulator of the electrophysiological substrates associated with AF.

The regulation of renal function by circadian gene BMAL1 has been recently recognized; however, the role and mechanism of BMAL1 in renal ischaemia-reperfusion injury (IRI) are still unknown. The purpose of this study was to clarify the pathophysiological role of BMAL1 in renal IRI. We measured the levels of BMAL1 and mitochondrial biogenesis-related proteins, including SIRT1, PGC-1α, NRF1 and TFAM, in rats with renal IRI. In rats, the level of BMAL1 decreased significantly, resulting in inhibition of SIRT1 expression and mitochondrial biogenesis. In addition, under hypoxia and reoxygenation (H/R) stimulation, BMAL1 knockdown decreased the level of SIRT1 and exacerbated the degree of mitochondrial damage and apoptosis. Overexpression of BMAL1 alleviated H/R-induced injury. Furthermore, application of the SIRT1 inhibitor EX527 not only reduced the activities of SIRT1 and PGC-1α but also further aggravated mitochondrial dysfunction and partially reversed the protective effect of BMAL1 overexpression. Moreover, whether in vivo or in vitro, the application of SIRT1 agonist resveratrol rescued the mitochondrial dysfunction caused by H/R or IRI by activating mitochondrial biogenesis. These results indicate that BMAL1 is a key circadian gene that mediates mitochondrial homeostasis in renal IRI through the SIRT1/PGC-1α axis, which provides a new direction for targeted therapy for renal IRI.

The main cause of death in patients with non-small cell lung cancer (NSCLC) is the progression of cancer metastasis, which can be attributed to multiple factors, such as cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) play important roles in the regulation of the cell cycle, cell proliferation, immune responses, and metastasis in cancers, but the potential roles and mechanisms of lincRNAs in CSC-like properties of cancer have not yet been elucidated.

Subarachnoid hemorrhage (SAH) elicits destruction of neuronal cells and neurological function, which is exacerbated by neuro-inflammation in EBI, and toll-like receptor 4 (TLR4) plays an important role in inflammatory cascade via modulation microglia polarization. Curcumin (Cur), as a natural phytochemical compound, has the potential characteristics on anti-inflammatory and microglia phenotype transformation. In this study, we verified the hypothesis curcumin promotes M2 polarization to inhibiting neuro-inflammation, which through suppressing TLR4 signaling pathway after SAH. In tlr4-/- mice and wild type (WT) subjected to prechiasmatic cistern blood injection, Western blotting, brain water content, neurological score, enzyme-linked immunosorbent assay (ELISA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed to investigate the role of TLR4 on neuro-inflammation response and microglia polarization. Curcumin with three different concentrations (50 mg/kg, 100 mg/kg and 200 mg/kg) were injected intraperitoneally (i.p.) at 15 min after SAH. The levels of TLR4, myeloid differentiation factor 88 (MyD88), nuclear factor- κB (NF-κB), Iba-1, CD86, CD206 and pro/anti-inflammation cytokines were measured by Western blotting and immunofluorescence staining at 24 h after SAH. SAH induction increased the protein levels of TLR4, pro-inflammation cytokines and proportion of M1 phenotype. Curcumin with 100 mg/kg treatment dramatically inhibited the release of pro-inflammatory mediators, and elevated the protein levels of anti-inflammatory cytokines and promoted microglia switch to M2. Meanwhile, curcumin treatment also decreased the expressions of TLR4, Myd88 and NF-κB at 24 h post SAH. TLR4 deficiency ameliorated brain water content, neurological deficit and reduced pro-inflammation cytokines after SAH. Moreover, curcumin treatment in tlr4-/- mice further induced M2 polarization, while had no statistic difference on brain water content and neurological score at 24 h post SAH. Our results indicated that curcumin treatment alleviated neuro-inflammation response through promoting microglia phenotype shift toward M2, and which might inhibiting TLR4/MyD88/NF-κB signaling pathway after SAH.

Radioiodine is a routine therapy for differentiated thyroid cancers. Non-thyroid cancers may be treated with radio-iodine following transfection with the human sodium/iodide symporter (hNIS) gene. The glial fibrillary acidic protein (GFAP) promoter is an effective tumor-specific promoter for gene expression and thus may be useful in targeted gene therapy of malignant glioma. The present study used GFAP promoter-modulated expression of the hNIS gene in an experimental model of radioiodine-based treatment for malignant glioma. Cells were transfected using a recombination adeno-virus and evaluated in cells by studying the transfected transgene expression through western blot analysis, (125)I uptake and efflux, clonogenicity following (131)I treatment and radioiodine therapy using a U87 xenograft nude mouse model. Following transfection with the hNIS gene, the cells showed 95-70-fold higher (125)I uptake compared with the control cells transfected with Ad-cytomegalovirus (CMV)-enhanced green fluorescent protein (EGFP). The western blotting revealed bands of ∼70, 49 and 43 kDa, consistent with the hNIS, GFAP and β-actin proteins. The clonogenic assay indicated that, following exposure to 500 μCi of (131)I-iodide for 12 h, >90% of cells transfected with the hNIS gene were killed. Ad-GFAP-hNIS-transfected and 2 mCi (131)I-injected U87 xenograft nude mice survived the longest of the three groups. The hNIS-expressing tumor tissue accumulated (99m)TcO(4) rapidly within 30 min of it being intraperitoneally injected. The experiments demonstrated that effective (131)I therapy was achieved in the malignant glioma cell lines following the induction of tumor-specific iodide uptake activity by GFAP promoter-directed hNIS gene expression in vitro and in vivo. (131)I therapy retarded Ad-GFAP-hNIS transfected-tumor growth following injection with (131)I in U87 xenograft-bearing nude mice.

Microparticles (MPs, ~size between 0.1 and 1 mm) are lipid encased containers derived from intact cells which contain antigen from the parent cells. MPs are involved in intercellular communication and regulate inflammation. Stroke increases secretion of brain derived MP (BDMP) which activate macrophages/microglia and induce neuroinflammation. Lactadherin (Milk fat globule-EGF factor-8) binds to anionic phospholipids and extracellular matrices, promotes apoptotic cell clearance and limits pathogenic antigen cross presentation. In this study, we investigate whether BDMP affects stroke-induced neuroinflammation and whether Lactadherin treatment reduces stroke initiated BDMP-induced neuroinflammation, thereby improving functional outcome after stroke. Middle aged (8-9 months old) male C57BL/6J mice were subjected to distal middle cerebral artery occlusion (dMCAo) stroke, and BDMPs were extracted from ischemic brain 24 h after dMCAo by ultracentrifugation. Adult male C57BL/6J mice were subjected to dMCAo and treated via tail vein injection at 3 h after stroke with: (A) +PBS (n = 5/group); (B) +BDMPs (1.5 × 108, n = 6/group); (C) +Lactadherin (400 μg/kg, n = 5/group); (D) +BDMP+Lactadherin (n = 6/group). A battery of neurological function tests were performed and mice sacrificed for immunostaining at 14 days after stroke. Blood plasma was used for Western blot assay. Our data indicate: (1) treatment of Stroke with BDMP significantly increases lesion volume, neurological deficits, blood brain barrier (BBB) leakage, microglial activation, inflammatory cell infiltration (CD45, microglia/macrophages, and neutrophils) into brain, inflammatory factor (TNFα, IL6, and IL1β) expression in brain, increases axon/white matter (WM) damage identified by decreased axon and myelin density, and increases inflammatory factor expression in the plasma when compared to PBS treated stroke mice; (2) when compared to PBS and BDMP treated stroke mice, Lactadherin and BDMP+Lactadherin treatment significantly improves neurological outcome, and decreases lesion volume, BBB leakage, axon/WM injury, inflammatory cell infiltration and inflammatory factor expression in the ischemic brain, respectively. Lactadherin treatment significantly increases anti-inflammatory factor (IL10) expression in ischemic brain and decreases IL1β expression in plasma compared to PBS and BDMP treated stroke mice, respectively. BDMP increases neuroinflammation and aggravates ischemic brain damage after stroke. Thus, Lactadherin exerts anti-inflammatory effects and improves the clearance of MPs to reduce stroke and BDMP induced neurological deficits.

Postnatal development of skeletal muscle is a highly dynamic period of tissue remodeling. Here, we used RNA-seq to identify transcriptome changes from late embryonic to adult mouse muscle and demonstrate that alternative splicing developmental transitions impact muscle physiology. The first 2 weeks after birth are particularly dynamic for differential gene expression and alternative splicing transitions, and calcium-handling functions are significantly enriched among genes that undergo alternative splicing. We focused on the postnatal splicing transitions of the three calcineurin A genes, calcium-dependent phosphatases that regulate multiple aspects of muscle biology. Redirected splicing of calcineurin A to the fetal isoforms in adult muscle and in differentiated C2C12 slows the timing of muscle relaxation, promotes nuclear localization of calcineurin target Nfatc3, and/or affects expression of Nfatc transcription targets. The results demonstrate a previously unknown specificity of calcineurin isoforms as well as the broader impact of alternative splicing during muscle postnatal development.

Ticks are medically-important arthropods that maintain and transmit numerous emerging viruses. China suffers severely from tick-borne viral diseases such as tick-borne encephalitis and severe fever with thrombocytopenia syndrome (SFTS), but the background of tick-borne viruses is very limited. Here we report the virome profiling of ticks and goat sera from SFTS-epidemic areas, and serological investigation of SFTS virus (SFTSV) and Nairobi sheep disease virus (NSDV). Results revealed divergent viruses in ticks and goat sera, including SFTSV and NSDV. Sequence and phylogenetic analyses showed that the SFTSV identified here was most closely related to human SFTSV in sampling and surrounding areas, and the NSDV to the previously identified NSDV from northeast China. Serological investigation of SFTSV infection in goats revealed intensive activity in those areas. Surprisingly, two different methods of NSDV serological investigation showed no sera positive for this virus.

Inflammation and autophagy occur during hepatic fibrosis development caused by various pathogens, and effectively curbing of autophage may delay the occurrence of hepatic fibrosis. The current study aimed to unravel the inhibitory effects of Ginsenoside Rg3 (G-Rg3) on inflammation-mediated hepatic autophagy to curb hepatic fibrosis caused by thioacetamide (TAA)-induced subacute and chronic hepatic injury. TAA is mainly metabolized in the liver to cause liver dysfunction. After intraperitoneal injection of TAA for 4 or 10 weeks (TAA-chronic mouse models), severe inflammatory infiltration and fibrosis occurred in the liver. Treatment with G-Rg3 alleviated hepatic pathological changes and reversed hepatic fibrosis in the TAA-chronic models with decreased deposition of collagen fibers, reduced expression of HSCs activation marker (α-SMA), and reduced secretion of profibrogenic factors (TGF-β1). G-Rg3 decreased expressions of autophagy-related proteins in mice of TAA-chronic models. Notably, G-Rg3 inhibited the survival of activated rat hepatic stellate cells (HSC-T6), but had no cytotoxicity on human hepatocytes (L02 cell lines). G-Rg3 dose-dependently inhibited autophagy in vitro with less expression of p62 and fewer LC3a transformation into LC3b in inflammatory inducer lipopolysaccharide (LPS)-induced rat HSC-T6 cells. Furthermore, G-Rg3 enhanced the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in vivo and in vitro. Besides, mTOR inhibitor Rapamycin and PI3K inhibitors LY294002 were employed in LPS-treated HSC-T6 cell cultures to verify that Rg3 partially reversed the increase in autophagy in hepatic fibrosis in vitro. Taken together, G-Rg3 exerted anti-fibrosis effect through the inhibition of autophagy in TAA-treated mice and LPS-stimulated HSC-T6 cells. These data collectively unravel that G-Rg3 may serve a promising anti-hepatic fibrosis drug.

Schizophrenia and bipolar disorder (BD) are believed to share clinical symptoms, genetic risk, etiological factors, and pathogenic mechanisms. We previously reported that single nucleotide polymorphisms spanning chromosome 3p21.1 showed significant associations with both schizophrenia and BD, and a risk SNP rs2251219 was in linkage disequilibrium with a human specific Alu polymorphism rs71052682, which showed enhancer effects on transcriptional activities using luciferase reporter assays in U251 and U87MG cells.

RNA-binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development by regulating premRNA splicing and mRNA stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remain unclear. In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that a higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted BC cell proliferation, while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanistically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and suppressing the transcription of miR-625-5p, which directly targets RBM24 and suppresses RBM24 expression. RBM24-regulated BC cell proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop. These results indicate that the RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop participates in BC progression. Disruption of this pathway may be a potential therapeutic strategy for BC treatment.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated mortality worldwide. Thus, there is an urgent requirement to identify novel diagnostic and prognostic biomarkers for this disease. The present study aimed to identify the hub genes associated with the progression and prognosis of patients with HCC. A total of three expression profiles of HCC tissues were extracted from the Gene Expression Omnibus (GEO) database, followed by the identification of differentially expressed genes (DEGs) using the GEO2R method. The identified DEGs were assessed for survival significance using Kaplan-Meier analysis. Among the 15 identified DEGs in HCC tissues [cytochrome P450 family 39 subfamily A member 1, cysteine rich angiogenic inducer 61, Fos proto-oncogene, forkhead transcription factor 1 (FOXO1), growth arrest and DNA damage inducible β, Inhibitor of DNA binding 1, interleukin-1 receptor accessory protein, metallothionein-1M, pleckstrin homology-like domain family A member 1, Rho family GTPase 3, serine dehydratase, suppressor of cytokine signaling 2 (SOCS2), tyrosine aminotransferase (TAT), S100 calcium-binding protein P and serine protease inhibitor Kazal-type 1 (SPINK1)]. Low expression levels of FOXO1, SOCS2 and TAT and high SPINK1 expression indicated poor survival outcomes for patients with HCC. In addition, SOCS2 was associated with distinct stages of HCC progression in patients and presented optimal diagnostic value. In vitro functional experiments indicated that overexpression of SOCS2 inhibited HCC cell proliferation and migration. Taken together, the results of the present study suggest that SOCS2 may act as a valuable prognostic marker that is closely associated with HCC progression.

Disintegrin and metalloproteinase domain-containing proteins (ADAMs) have been implicated in cell adhesion, signaling and migration. The aim of the present study was to identify key members of the ADAM protein family associated with the metastasis of gastric cancer and to evaluate their clinical significance. A total of 193 patients with gastric cancer and positive lymph node metastasis were enrolled. Key members of the ADAM family associated with lymph node metastasis were identified. The correlations between survival times and the clinicopathological features of patients were investigated. Furthermore, ADAM17 expression in gastric cancer cells with different metastatic potentials was determined. ADAM17 was overexpressed in BGC‑823 cells and suppressed in SGC‑7901 cells to further investigate its effects on cell viability and migration. The key pathways associated with ADAM17 were identified by gene set enrichment analysis (GSEA). It was found that ADAM9 and ADAM17 were significantly upregulated in gastric cancer and positive metastatic lymph node tissues. Further, there was a strong correlation between the survival times of patients and ADAM17 expression. ADAM17 was upregulated in gastric cancer cells with high metastatic potential. The viability of BGC‑823 cells significantly increased following ADAM17 overexpression, whereas the viability and migration of SGC‑7901 cells decreased following ADAM17 suppression. GSEA and western blot analysis revealed a positive correlation between the Notch and Wnt signaling pathways with ADAM17 expression. In conclusion, the increased expression of ADAM17 promoted the progression of gastric cancer, potentially via Notch and/or Wnt signaling pathway activation, and ADAM17 may serve as a useful prognostic marker.

Breast cancer is one of the most common and serious types of cancer, with a particularly unfavorable prognosis. Although dysregulation of β-galactoside α 2,6-sialyltransferase 2 (ST6GAL2) has been observed in multiple cancers, the mechanism involved remains to be clarified. In this study, we focused on the potential function of ST6GAL2 in the regulation of breast cancer.