Abstract Although PARP inhibitors are approved for breast cancer patients with germline mutations in BRCA1/2, usage fails to extend overall survival or promote the efficacy of immunotherapy, despite preclinical evidence that PARP inhibitors promote T cell-mediated immunity through activation of the cGAS-STING pathway. Here we show that tumor ectonucleotidase ENPP1, through its ability to degrade extracellular 2’3’-cGAMP, is a potent suppressor of T cell infiltration and effector function in preclinical models of Brca1-deficient disease. Deletion or therapeutic targeting of ENPP1 with a novel blocking nanobody improved tumor control and unleashed the combinatorial efficacy of PARP inhibitors and anti-PD1 immunotherapy. Both tumor and host STING were required for tumor control, with macrophage STING signaling reducing their suppressive capacity and tumor STING promoting antigen presentation. ENPP1 expression negatively correlates with overall survival and response to PARP inhibition in patients with homologous repair deficiency, in addition to regulating the efficacy of chemoimmunotherapy, highlighting its therapeutic potential. Citation Format: Jie Li, Charlotte Mason, Kay Hänggi, Achintyan Gangadharan, Xing Qingyu, Olabisi Osunmakinde, Xiaoxian Liu, Daiana Celias, Alyssa Obermayer, Tao Li, Conor C. Lynch, Timothy I. Shaw, Justin M. Lopchuk, Xiaoqing Yu, Vincent C. Luca, Brian Ruffell. Homologous recombination deficiency sensitizes breast cancer to therapeutic targeting of the ectonucleotidase ENPP1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB402.

Abstract Radiosensitizers that improve tumor-cell responses to radiation without increasing normal-tissue toxicity are needed in colorectal cancer (CRC). We investigated whether inhibition of ataxia telangiectasia and Rad3-related (ATR) kinase by VE-822 (berzosertib) enhances radiation response and whether p53 status is associated with the magnitude of response. HCT116 (p53 wild type), HT29 (p53 mutant), and HCT116 cells with siRNA-mediated p53 knockdown (HCT116 KD) were treated with VE-822 with or without ionizing radiation (RT). Short-term cell viability and long-term clonogenic survival were evaluated. DNA-damage signaling and ATR-pathway activity were assessed by analysis of γH2AX and phosphorylated CHK1, whereas flow cytometry was used to examine cell-cycle distribution, mitotic entry, and apoptosis. VE-822 IC50 values were 80.8 nM for HCT116, 33.6 nM for HT29, and 19.6 nM for HCT116 KD cells. A low concentration of VE-822 (20 nM, administered 1 h before RT) had minimal effects in HCT116 cells but reduced viability and clonogenic survival in HCT116 KD cells, particularly when combined with RT. VE-822 reduced pCHK1 and was associated with sustained γH2AX signaling, with more pronounced effects in HCT116 KD cells. At 24 h after RT, HCT116 cells predominantly accumulated in G1 with modest apoptosis, whereas HCT116 KD cells showed greater G2/M accumulation and apoptosis after VE-822 plus RT. Increased phospho-Histone H3 positivity after combined treatment was consistent with increased mitotic entry. These in vitro findings suggest that impaired p53 function is associated with increased sensitivity to combined ATR inhibition and irradiation and support further evaluation of p53 status as a candidate response biomarker.

Irbesartan improves ventricular remodeling (VR) following myocardial infarction (MI). This study investigates whether irbesartan attenuates VR by reducing aldosterone production in the heart and its underlying mechanisms. MI was induced in male Sprague-Dawley rats through coronary artery ligation. The MI rats were randomly assigned to two groups: one received a vehicle, and the other received 100 mg/kg/day of irbesartan for 5 weeks. Cardiac function and myocardial fibrosis were assessed using echocardiography and Masson's trichrome staining, respectively. The impact of angiotensin II (Ang II) stimulation on cardiac microvascular endothelial cells (CMECs) from commercial sources was determined using ELISA, real-time PCR, and Western blotting. Irbesartan reduced left ventricular mass index, collagen composition, and aldosterone levels while enhancing cardiac function in MI rats. In vitro, Ang II time-dependently stimulated aldosterone secretion and CYP11B2 mRNA expression in CMECs (p < 0.05). Additionally, Ang II significantly upregulated p-CREB protein levels. However, these effects were abrogated by irbesartan and partially attenuated by CaMK inhibitor KN93 (p < 0.05). In conclusion, our study demonstrated that improvement in VR by irbesartan coincided with reduced CREB phosphorylation in CMECs and reduced aldosterone synthesis in the non-infarcted tissue. These effects may be mediated by blocking the AT1 receptor.

Atherosclerosis, a life-threatening complication of diabetes mellitus (DM), significantly increases the mortality risk among diabetic patients. Vascular smooth muscle cells (VSMCs) not only constitute the core of atherosclerotic lesions but also serve as primary components of plaques. Although diabetes expedites this transformation process, the specific mechanism remains elusive. Traditional proteomic approaches that analyze average signals of all cells overlook the importance of spatial information, although different cells within the same tissue exhibit distinct molecular characteristics during various stages of atherosclerosis progression. In this study, we employed spatial proteomic technology to comprehensively analyze proteins in vascular smooth muscle tissues and atherosclerotic plaques obtained from a mouse model of atherosclerosis and DM complicated with arteriosclerosis. We also employed RNA sequencing technology to further investigate the changes in RNA alternative splicing in atherosclerosis and DM complicated with arteriosclerosis in cell models. Our findings revealed the reduced expression of Nup93 within VSMCs under combined high glucose and ox-LDL stimulation, mimicking diabetic atherosclerotic stress. This reduction impairs the nuclear import of splicing regulators SRSF1 and SRSF3, leading to abnormal alternative splicing of SerpinE2, which in turn enhances its mRNA stability and promotes VSMCs' proliferation. These results reveal a novel mechanistic axis whereby diabetic atherosclerotic stress drives VSMCs dysfunction through Nup93-mediated splicing dysregulation, offering new molecular targets for the treatment of diabetes-associated atherosclerosis.

Objective Human Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. Methods RNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. Results We revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. Conclusion Our study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly

Mitochondrial damage is an early and key marker of neuronal damage in prion diseases. As a process involved in mitochondrial quality control, mitochondrial biogenesis regulates mitochondrial homeostasis in neurons and promotes neuron health by increasing the number of effective mitochondria in the cytoplasm. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates neuronal mitochondrial biogenesis and quality control in neurodegenerative diseases via deacetylation of a variety of substrates. In a cellular model of prion diseases, we found that both SIRT1 protein levels and deacetylase activity decreased, and SIRT1 overexpression and activation significantly ameliorated mitochondrial morphological damage and dysfunction caused by the neurotoxic peptide PrP106–126. Moreover, we found that mitochondrial biogenesis was impaired, and SIRT1 overexpression and activation alleviated PrP106–126-induced impairment of mitochondrial biogenesis in N2a cells. Further studies in PrP106–126-treated N2a cells revealed that SIRT1 regulates mitochondrial biogenesis through the PGC-1α-TFAM pathway. Finally, we showed that resveratrol resolved PrP106–126-induced mitochondrial dysfunction and cell apoptosis by promoting mitochondrial biogenesis through activation of the SIRT1-dependent PGC-1α/TFAM signaling pathway in N2a cells. Taken together, our findings further describe SIRT1 regulation of mitochondrial biogenesis and improve our understanding of mitochondria-related pathogenesis in prion diseases. Our findings support further investigation of SIRT1 as a potential target for therapeutic intervention of prion diseases.

IntroductionDifferent studies provide conflicting evidence regarding the potential for glucocorticoids (GCs) to increase the risk of cardiovascular diseases. This study performed a systematic review and meta-analysis to determine the correlation between GCs and cardiovascular risk, including major adverse cardiovascular events (MACE), death from any cause, coronary heart disease (CHD), heart failure (HF), and stroke.MethodsWe performed a comprehensive search in PubMed and Embase (from inception to June 1, 2022). Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.ResultsA total of 43 studies with 15,572,512 subjects were included. Patients taking GCs had a higher risk of MACE (RR = 1.27, 95% CI: 1.15-1.40), CHD (RR = 1.25, 95% CI: 1.11-1.41), and HF (RR = 1.92, 95% CI: 1.51-2.45). The MACE risk increased by 10% (95% CI: 6%-15%) for each additional gram of GCs cumulative dose or by 63% (95% CI: 46%-83%) for an additional 10 & mu;g daily dose. The subgroup analysis suggested that not inhaled GCs and current GCs use were associated with increasing MACE risk. Similarly, GCs were linked to an increase in absolute MACE risk of 13.94 (95% CI: 10.29-17.58) cases per 1,000 person-years.ConclusionsAdministration of GCs is possibly related with increased risk for MACE, CHD, and HF but not increased all-cause death or stroke. Furthermore, it seems that the risk of MACE increased with increasing cumulative or daily dose of GCs.

PURPOSE:Pathologic complete response (pCR) rates of patients with triple-negative breast cancer who were administered docetaxel plus carboplatin were significantly higher than those of patients administered epirubicin/cyclophosphamide followed by docetaxel in the neoadjuvant NeoCART trial. Here, we performed a preplanned secondary analysis of the homologous recombination deficiency (HRD) score as a predictor of the pCR in patients with triple-negative breast cancer from the NeoCART cohort.METHODS:Pretherapeutic tumor tissues were assessed retrospectively by DNA extraction and sequencing. BRCA1/2 mutations were evaluated in both somatic and germline forms. HRD scores were calculated from genome-wide allele-specific copy number results and comprised telomeric allelic imbalance, loss of heterozygosity, and large-scale state transitions. High HRD scores were defined as ≥ 38, and HRD was defined as either a high HRD score or a deleterious BRCA1/2 mutation.RESULTS:HRD testing was completed for 43 (79.6%) of 54 NeoCART cohort patients. Thirty of 43 (69.8%) tumors had high HRD scores, and eight patients had BRCA-mutated tumors. No significant association between BRCA1/2 mutation status and pCR was observed either in the general population or in the two treatment arms. Docetaxel plus carboplatin group patients who achieved pCR had higher HRD scores than non-pCR patients, and this difference approached significance (61.69 ± 24.26 v 39.44 ± 22.83, P = .061). No significant correlations between HRD scores and pCR (61.29 ± 24.02 v 53.21 ± 24.31, P = .480) or residual cancer burden 0/1 (62.50 ± 22.50 v 51.85 ± 24.74, P = .324) were observed in the epirubicin/cyclophosphamide followed by docetaxel group.CONCLUSION:HRD is a potential predictive biomarker for clinical benefit from neoadjuvant carboplatin-based chemotherapy and provides a possibility for screening the optimum chemotherapy backbone to combine with immunotherapy.

Many traditional Chinese herbs contain pyrrolizidine alkaloids (PAs), which have been reported to be toxic to livestock and humans. However, the lack of PAs standards makes it difficult to effectively conduct a risk assessment in the varied components of traditional Chinese medicine. It is necessary to propose a suitable strategy to obtain the representative occurrence data of PAs in complex systems. A comprehensive approach for annotating the structures, concentration, and mutagenicity of PAs in three Chinese herbs has been proposed in this article. First, feature-based molecular networking (FBMN) combined with network annotation propagation (NAP) on the Global Natural Products Social Molecular Networking web platform speeds up the process of annotating PAs found in Chinese herbs. Second, a semi-quantitative prediction model based on the quantitative structure and ionization intensity relationship (QSIIR) is used to forecast the amounts of PAs in complex substrates. Finally, the T.E.S.T. was used to provide predictions regarding the mutagenicity of annotated PAs. The goal of this study was to develop a strategy for combining the results of several computer models for PA screening to conduct a comprehensive analysis of PAs, which is a crucial step in risk assessment of unknown PAs in traditional Chinese herbal preparations.

Summary: The reported incidence of arterial thromboembolism (ATE) and venous thromboembolism (VTE) after cancer varies.Methods: We performed a meta-analysis to define the incidence of thromboembolism (TE) in cancer patients. Articles were searched in PubMed and Embase from inception to April 1, 2022. Studies reporting the incidence data or data from which incidence could be estimated among patients with cancer and the explicit follow-up duration were included. Articles were excluded if they were cross-sectional studies, review articles, commentaries, case reports or editorials. Studies involving a population receiving a specific or single treatment and primary studies with a small sample size (<100 participants) were also excluded. This meta-analysis was conducted in accordance with the Meta-analyses and Systematic reviews of Observational Studies (MOOSE). Data were abstracted by two investigators from included studies. The primary outcome of this analysis was the incidence of TE events, including ATE and VTE. The incidence of ATE and VTE in cancer patients was expressed as per 1000 person-years of follow-up. (PROSPERO CRD42021272276)Findings: Seventy-four studies involving 5059134 cancer patients were identified. The incidence rate per 1000 person-years was 11·66 (95% CI 7·68-15·64) for ATE, 26·32 (95% CI 24·46-28·18) for VTE. In addition, the highest incidence of ATE was observed in patients with gastrointestinal cancer, while patients with pancreatic cancer had the highest incidence of VTE. The risk of ATE and VTE increased at the initial stage of cancer, and then declined and became non-significant.Interpretation: This meta-analysis provided overall estimates of ATE and VTE incidence in cancer patients, adding an important insight into the trajectory of the development of TE in cancer patients, which could help reduce the risk of TE in cancer patients in the future.Funding: None to declare. Declaration of Interest: We declare no competing interests.

Argonaute proteins, which consist of AGO1, AGO2, AGO3 and AGO4, are key players in microRNA-mediated gene silencing. So far, few non-microRNA related biological roles of AGO4 have been reported. Here, we first found that AGO4 had low expression in non-small cell lung cancer (NSCLC) patient tumor tissues and could suppress NSCLC cell proliferation and metastasis. Subsequent studies on the mechanism showed that AGO4 could interact with the tripartite motif-containing protein 21 (TRIM21) and the glucose-regulated protein 78 (GRP78). AGO4 promoted ubiquitination of GRP78 by stabilizing TRIM21, a new specific ubiquitin E3 ligase for promoting K48-linked polyubiquitination of GRP78 confirmed in this paper, which resulted in induced cell apoptosis and inhibited autophagy by activating mTOR signal pathway. Further studies showed that p53 had dominant effects on TRIM21-GRP78 axis by directly increasing the expression of TRIM21 in p53 wild-type cells and AGO4 may alternatively regulate TRIM21-GRP78 axis in p53-deficient cells. We also found that overexpression of AGO4 results in suppression of multiple p53-deficient cell growth both in vivo and vitro. Together, we showed for the first time that the AGO4-TRIM21-GRP78 axis, as a new regulatory pathway, may be a novel potential therapeutic target for p53-deficient tumor treatment.

PI3K/AKT/mTOR pathway plays important roles in cancer development, and the negative role of PTEN in the PI3K/AKT/mTOR pathway is well known, but whether PTEN can be inversely regulated by PI3K/AKT/mTOR has rarely been reported. Here we aim to investigate the potential regulatory relationship between PTEN and Akt/mTOR inhibition in MEFs. AKT1 E17K and TSC2 -/- MEFs were treated with the AKT inhibitor MK2206 and the mTOR inhibitors rapamycin and Torin2. Our results reveal that inhibition of AKT or mTOR suppresses PTEN expression in AKT1 E17K and TSC2 -/- MEFs, but the transcription, subcellular localization, eIF4E-dependent translational initiation or lysosome- and proteasome-mediated degradation of PTEN change little, as shown by the real time PCR, nucleus cytoplasm separation assay and immunofluorescence analysis. Moreover, mTOR suppression leads to augmentation of mouse PTEN-3'UTR-binding miRNAs, including miR-23a-3p, miR-23b-3p, miR-25-3p and miR-26a-5p, as shown by the dual luciferase reporter assay and miRNA array analysis, and miRNA inhibitors collaborately rescue the decline of PTEN level. Collectively, our findings confirm that inhibition of mTOR suppresses PTEN expression by upregulating miRNAs, provide a novel explanation for the limited efficacy of mTOR inhibitors in the treatment of mTOR activation-related tumors, and indicate that dual inhibition of mTOR and miRNA is a promising therapeutic strategy to overcome the resistance of mTOR-related cancer treatment.

Previous studies have shown that the addition of carboplatin to neoadjuvant chemotherapy improved the pathologic complete response (pCR) rate in patients suffering from triple-negative breast cancer (TNBC) and patients who obtained a pCR could achieve prolonged event-free survival (EFS) and overall survival (OS). However, no studies have assessed the effects of the combination of docetaxel and carboplatin without anthracycline with taxane-based and anthracycline-based regimens. The NeoCART study was designed as a multicenter, randomized controlled, open-label, phase II trial to assess the efficacy and safety of docetaxel combined with carboplatin in untreated stage II-III TNBC. All eligible patients were randomly assigned, at a 1:1 ratio, to an experimental docetaxel plus carboplatin (DCb) for six cycles group (DCb group) or an epirubicin plus cyclophosphamide for four cycles followed by docetaxel for four cycles group (EC-D group). PCR (ypT0/is ypN0) was evaluated as the primary outcome. Between 1 September 2016 and 31 December 2019, 93 patients were randomly assigned and 88 patients were evaluated for the primary endpoint (44 patients in each group). In the primary endpoint analysis, 27 patients in the DCb group (61.4%, 95% CI 47.0-75.8) and 17 patients in the EC-D group achieved a pCR (38.6%, 95% CI 24.3-53.0; odds ratio 2.52, 95% CI 2.4-43.1; P-noninferiority = .004). Noninferiority was met, and the DCb regimen was confirmed to be superior to the EC-D regimen (P = .044, superiority margin of 5%). At the end of the 37-month median follow-up period, OS and EFS rates were equivalent in both groups.

Our previous investigation indicated that angiotensin II (Ang II) enhances the expression of Kv1.5, a promising target for the treatment of atrial fibrillation (AF), by activating reactive oxygen species (ROS)-dependent phosphorylation of Smad 2/3 (forming P-Smad 2/3) and ERK 1/2 (forming P-ERK 1/2). A recent study indicated that aldosterone (Aldo) upregulates atrial Kv1.5 protein in a rat AF model, but the mechanism remains unknown. The present study aimed to clarify the mechanism underlying Aldo-induced Kv1.5 expression and to test whether spironolactone may modulate atrial Kv1.5. Our Western blot analysis indicated that the Aldo/mineralocorticoid receptor (MR) interacts with Ang II/AT1R in upregulating Kv1.5 expression in cultured neonatal atrial myocytes (NRAMs). Blockade of MR with spironolactone and of AT1R with losartan significantly suppressed Kv1.5 expression induction by combined Aldo and Ang II treatment. Aldo increased the protein expression of Nox1, Nox2 and Nox4, but this effect was abolished by spironolactone pretreatment. The Aldo-induced upregulation of Kv1.5 was also reversed by the Src protein tyrosine kinase family inhibitor PP2, the Nox2 inhibitor gp91ds-tat and the Nox1/Nox4 inhibitor GKT137831 but not by the Rac GTPase inhibitor NSC23766. Flow cytometry showed that the Aldo-induced ROS production was inhibited by spironolactone, PP2, gp91ds-tat and GKT137831. Spironolactone suppressed the Aldo-induced protein expression phosphorylated Src (P-Src), P-Smad 2/3 and P-ERK 1/2. In conclusion, we have demonstrated that spironolactone suppresses Aldo-induced Kv1.5 expression by attenuating MR-Nox1/2/4-mediated ROS generation in NRAMs.

Human vasorin (VASN) as a type I transmembrane protein, is a potential biomarker of hepatocellular carcinoma, which could expedite HepG2 cell proliferation and migration significantly in vitro. The ectodomain of VASN was proteolytically released to generate soluble VASN (sVASN), which was validated to be the active form. Among several monoclonal antibodies produced against sVASN, the clone V21 was found to bind with the recombinant human sVASN (rhsVASN) with the highest affinity and specificity, and also have inhibitory effects on proliferation and migration of HepG2 cells. Hence the phage-displayed peptide library was screened against the antibody V21. The positive phage clones were isolated and sequenced, and one unique consensus motifs was obtained. The result of sequence alignment showed that the conserved motif had similarity to VASN(Cys432-Cys441), embedded in the epidermal growth factor (EGF)-like domain. The synthetic mimotope peptide V21P1 and V21P2 were confirmed to bind with V21 and could compete with rhsVASN in ELISA assay. And they could also almost completely reverse the inhibitory effect of V21 on HepG2 migration and proliferation. Furthermore, the antibodies produced against V21P1 were able to bind not only with the peptide V21P1, but also with rhsVASN and the natural VASN from HepG2 cell. Our results showed that V21 seemed to be a functional antibody. The mimotopes toward V21 might mimic the functional domain of VASN, which would be helpful to exploit VASN functions and act as a candidate target for developing therapeutic antibodies against VASN.

Triple-negative breast cancer (TNBC) is the malignancy with the worst outcome among all breast cancer subtypes. We reported that ETV1 is a significant oncogene in TNBC tumourigenesis. Consequently, investigating the critical regulatory microRNAs (miRNAs) of ETV1 may be beneficial for TNBC targeted therapy.

LncRNA-GAS5 can act as a "sponge" for microRNA-21 (miR-21) by competitively sequestering miR-21 from binding target mRNAs. Moreover, miR-21 directly regulates PTEN and TPM1 via imperfect complementary target base pairing. We confirmed miR-21 regulates PTEN and TPM1 protein expression without significantly affecting PTEN and TPM1 mRNA expression via imperfect complementary target binding in HEK293T and HeLa cells. Furthermore, Overexpressing miR-21 could significantly shorten half-lives of PTEN and TPM1, miR-21 enhanced PTEN and TPM1 decay. Cells were transfected with 1ncRNA-GAS5 expression vector, we found 1ncRNA-GAS5 competitively bound miR-21 and increased the half-lives of PTEN and TPM1. Besides, miR-21 bound with 1ncRNA-GAS5 could lead rapid decay of 1ncRNA-GAS5. This study indicates 1ncRNA-GAS5 functions as a miR-21 "sponge" that inhibits mRNA degradation of the miR-21 imperfect complementary targets PTEN and TPM1, and miR-21 also could regulate lncRNA-GAS5 stability by base pairing. Further exploration of the mechanisms may improve our understanding of the IncRNA-miRNA-mRNA sophisticated regulatory feedback loop.

Objective: To evaluate protein profiles and Fc gamma receptor lib (FCGRIIB) expression in abdominal aortic aneurysm (AAA) compared to the expression in normal aortas. Methods: We performed a protein array to study the protein expression profiles within AAA and normal aortic tissues. FCGRIIB was found to be significantly elevated in AAA samples. Quantitative PCR and Western blot analyses were performed to study the expression of FCGRIIB in AAA compared to that in normal aortic tissue. Immunohistochemistry was used to locate FCGRIIB and the B cell marker CD19 in AAA and normal aortas specimens. Results: FCGRIIB was significantly elevated in AAA tissues in both mRNA (AAA vs. normal control: about 5.8 folds, p < 0.001) and protein levels (AAA vs. normal control: about 6.3 folds, p < 0.001). In AAA specimens, immunohistochemistry revealed that FCGRIIB localized to the area of inflammatory infiltrates, which consisted of CD 19(+) B cells and other inflammatory cells. FCGRIIB and CD19 were undetectable in normal aortas. Conclusions: FCGRIIB was significantly elevated in AAA tissues compared to normal aortas. FCGRIIB may be involved in the pathogenesis of AAA by regulation of inflammatory reactions. (C) 2017 Published by Elsevier Inc.

GADD45A (growth arrest and DNA damage inducible alpha), a stress response gene induced by genotoxic and nongenotoxic stresses, is implicated in various key processes, including the control of cell cycle checkpoints and DNA repair. The expression of GADD45A is directly regulated by numerous transcription factors, with p53 being the most representative. Moreover, post-transcriptional regulation also plays a role in GADD45A expression. However, little is known about the regulatory effects of microRNAs (miRNAs) on GADD45A expression. As a potential tumour suppressor, miR-138 has pleiotropic biological functions in various cancers. We have previously reported p53-mediated activation of miR-138 in human non-small-cell lung cancer (NSCLC) cells. In this study, we found that miR-138 specifically targeted AGO2, which affects the stability and maturation of miR-130b. Decreased expression of miR-130b promoted the expression of GADD45A and resulted in the G2/M phase arrest and proliferation inhibition in human NSCLC cells. Our results suggested that p53 could alternatively upregulate GADD45A in human NSCLC cells through a post-transcriptional pathway in which miR-138 is involved.