ALKBH5-mediated m6A modification of IL-11 drives macrophage-to-myofibroblast transition and pathological cardiac fibrosis in mice.

Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients.

Photo-sono activated BNT@MoS2 composites for rapid eradication of breast cancer.

Non-invasive external energy triggered efficient tumor therapy is a promising specific treatment strategy. Herein, a composite material of bismuth sodium titanate (BNT) and molybdenum disulfide (MoS2) with piezoelectric effect was designed for the synergistic treatment of breast cancer with near-infrared-II (NIR-II) light and ultrasound (US) activation. The BNT@MoS2 exhibit excellent photothermal and acoustic properties upon excitation by 1060 nm NIR-II laser and US, respectively. The synergistic effect of hyperthermia and reactive oxygen species (ROS) under photoacoustic action endows the BNT@MoS2 with remarkable anti-tumor activities, enabling them to eradicate breast cancer cells within 10 min. The work could provide new insights into the treatment of breast cancer.

First in-human evaluation of [1-13C]pyruvate in D2O for hyperpolarized MRI of the brain: A safety and feasibility study.

PURPOSE: To investigate the safety and value of hyperpolarized (HP) MRI of [1-13C]pyruvate in healthy volunteers using deuterium oxide (D2O) as a solvent. METHODS: Healthy volunteers (n = 5), were injected with HP [1-13C]pyruvate dissolved in D2O and imaged with a metabolite-specific 3D dual-echo dynamic EPI sequence at 3T at one site (Site 1). Volunteers were monitored following the procedure to assess safety. Image characteristics, including SNR, were compared to data acquired in a separate cohort using water as a solvent (n = 5) at another site (Site 2). The apparent spin-lattice relaxation time (T1) of [1-13C]pyruvate was determined both in vitro and in vivo from a mono-exponential fit to the image intensity at each time point of our dynamic data. RESULTS: All volunteers completed the study safely and reported no adverse effects. The use of D2O increased the T1 of [1-13C]pyruvate from 66.5 ± 1.6 s to 92.1 ± 5.1 s in vitro, which resulted in an increase in signal by a factor of 1.46 ± 0.03 at the time of injection (90 s after dissolution). The use of D2O also increased the apparent relaxation time of [1-13C]pyruvate by a factor of 1.4 ± 0.2 in vivo. After adjusting for inter-site SNR differences, the use of D2O was shown to increase image SNR by a factor of 2.6 ± 0.2 in humans. CONCLUSIONS: HP [1-13C]pyruvate in D2O is safe for human imaging and provides an increase in T1 and SNR that may improve image quality.

Metastatic Pleomorphic Lobular Carcinoma of the Breast to the Urinary Bladder: A Report of 10 Cases and Assessment of TRPS1 in the Differential Diagnosis With Plasmacytoid Urothelial Carcinoma.

CONTEXT.­: Metastatic pleomorphic lobular carcinoma (MPLC) to the bladder is rare and has considerable histologic and immunohistochemical overlap with plasmacytoid urothelial carcinoma (PUC). OBJECTIVE.­: To distinguish MPLC from PUC morphologically and immunohistochemically, including a newer marker, TRPS1. DESIGN.­: Ten MPLCs to the bladder were reassessed and stained with estrogen, progesterone, and androgen receptors; GATA3; keratin 5/6; HMWK; GCDFP-15; and TRPS1. Sixteen PUCs constituted controls. RESULTS.­: We studied 4 transurethral resections of bladder tumors and 6 biopsies from 10 women (median age, 69 years) who had breast cancer on average 15 years prior. Microscopic patterns included single cells and cords of cells (n = 4), nests/sheets of dyscohesive cells (n = 2), or both (n = 4). All tumors had cells with voluminous eosinophilic cytoplasm and eccentric nuclei mimicking PUC, and 7 of 10 tumors had signet ring cells. MPLCs were positive for estrogen (8 of 10), progesterone (3 of 7), and androgen receptors (4 of 10); GCDFP-15 (7 of 10); GATA3 (9 of 10); HMWK (7 of 8); and TRPS1 (7 of 10). No MPLCs stained for keratin 5/6 (n = 9). Of 16 PUCs, 2 showed faint and 2 demonstrated strong TRSP1 staining; 7 of 16 were negative for p63. CONCLUSIONS.­: MPLC to bladder often presents in patients with a remote history of breast cancer, exhibiting significant histologic and immunohistochemical overlap with PUC. Based on prior works and the current study, estrogen receptor (particularly SP-1), mammaglobin, and p63 help differentiate MPLC from PUC. Keratin 5/6 may aid in distinguishing a less frequent basal type PUC because it is typically negative in MPLC. Some PUCs express TRPS1. Caution should be exercised because immunophenotypes of these tumors greatly overlap, and ramifications of misclassification are major.

The Characteristics of Macrophage Heterogeneity in Atherosclerotic Aortas.

Macrophage is the main effector cell during atherosclerosis. We applied single-cell RNA sequencing (scRNA) data to investigate the role of macrophage subsets in atherosclerosis. Monocyte and macrophage clusters were divided into 6 subclusters. Each subcluster's markers were calculated and validated by immunofluorescence. Elevated macrophage subclusters in the WD group were subject to enrichment pathway analysis and exhibited different phenotypes. Pseudotime analysis shows the subclusters originate from monocytes. We cultured bone marrow-derived macrophages with CSF-1 and ox-LDL to simulate an atherosclerotic-like environment and detected the transformation of subclusters. Macrophage-Vegfa and Macrophage-C1qb increased in the WD group. Macrophage-Vegfa acquires the characteristics of phagocytosis and immune response, while Macrophage-C1qb is not involved in lipid metabolism. The two subclusters are both enriched in cell movement and migration pathways. Experimental verification proved Monocyte-Ly6C evolved into Macrophage-Vegfa and Macrophage-C1qb during atherosclerosis progression.

An ascorbic acid-decorated nanostructured surface on titanium inhibits breast cancer development and promotes osteogenesis.

The chest wall is the most frequent metastatic site of breast cancer (BC) and the metastasis usually occurs in a solitary setting. Chest wall resection is a way to treat solitary BC metastasis, but intraoperative bone defects and local tumor recurrence still affect the life quality of patients. Titanium-based prostheses are widely used for chest wall repair and reconstruction, but their inherent bio-inertness makes their clinical performance unfavorable. Nanostructured surfaces can give titanium substrates the ability to excellently modulate a variety of cellular functions. Ascorbic acid is a potential stimulator of tumor suppression and osteogenic differentiation. An ascorbic acid-decorated nanostructured titanium surface was prepared through alkali treatment and spin-coating technique and its effects on the biological responses of BC cells and osteoblasts were assessed. The results exhibited that the nanorod structure and ascorbic acid synergistically inhibited the proliferation, spreading, and migration of BC cells. Additionally, the ascorbic acid-decorated nanostructured surface significantly promoted the proliferation and osteogenic differentiation of osteoblasts. This work may provide valuable references for the clinical application of titanium materials in chest wall reconstruction after the resection of metastatic BC.

A multifunctional nano-hydroxyapatite/MXene scaffold for the photothermal/dynamic treatment of bone tumours and simultaneous tissue regeneration.

After resection of bone tumour, the risk of cancer recurrence and numerous bone defects continues to threaten the health of patients. To overcome the challenge, we developed a novel multifunctional scaffold material consisting mainly of nano-hydroxyapatite particles (n-HA), MXene nanosheets and g-C3N4 to prevent tumour recurrence and promote bone formation. N-HA has the potential to restrict the growth of osteosarcoma cells, and the combination of MXene and g-C3N4 enables the scaffolds to produce photodynamic and photothermal effects simultaneously under near infrared (NIR) irradiation. Surprisingly, n-HA can further enhance the synergistic anti-tumour function of photodynamic and photothermal, and the scaffolds can eradicate osteosarcoma cells in only 10 min at a mild temperature of 45 ℃. Moreover, the scaffold exhibit exceptional cytocompatibility and possesses the capacity to induce osteogenic differentiation of bone marrow mesenchymal stem cells. Therefore, this multifunctional scaffold can not only inhibits the proliferation of bone tumour cells and rapidly eradicate bone tumour through NIR irradiation, but also enhances osteogenic activity. This promising measure can be used to treat tissue damage after bone tumour resection.

Quantifying Atomically Dispersed Catalysts Using Deep Learning Assisted Microscopy.

The catalytic performance of atomically dispersed catalysts (ADCs) is greatly influenced by their atomic configurations, such as atom-atom distances, clustering of atoms into dimers and trimers, and their distributions. Scanning transmission electron microscopy (STEM) is a powerful technique for imaging ADCs at the atomic scale; however, most STEM analyses of ADCs thus far have relied on human labeling, making it difficult to analyze large data sets. Here, we introduce a convolutional neural network (CNN)-based algorithm capable of quantifying the spatial arrangement of different adatom configurations. The algorithm was tested on different ADCs with varying support crystallinity and homogeneity. Results show that our algorithm can accurately identify atom positions and effectively analyze large data sets. This work provides a robust method to overcome a major bottleneck in STEM analysis for ADC catalyst research. We highlight the potential of this method to serve as an on-the-fly analysis tool for catalysts in future in situ microscopy experiments.

A Cytidine-Modified surfactant anchored liquid crystal Droplet-Based sensor for rapid and accurate detection of silver ions.

Liquid crystal (LC) droplets exhibit unique and sensitive response behaviors to surface absorptions, making them promising candidates for sensing aplications. Here, we have developed a label-free, portable, and cost-effective sensor for the specific and rapid detection of silver ions (Ag+) in drinking-water samples. To achieve this, we have modified cytidine into a surfactant (denoted as C10-M-C) and anchored it onto the surface of LC droplets. The specific binding ability between cytidine and Ag+ enables LC droplets anchored with C10-M-C to respond rapidly and specifically to Ag+ ions. Furthermore, the sensitivity of the response meets requirements for the harmless concentration of Ag+ in drinking-water. The sensor we developed is label-free, portable, and cost-effectively. We believe that the sensor reported here can be applied to the detection of Ag+ in drinking-water and environmental samples.

[6,6'-2 H2 ] fructose as a deuterium metabolic imaging probe in liver cancer.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. Imaging plays a crucial role in the early detection of HCC, although current methods are limited in their ability to characterize liver lesions. Most recently, deuterium metabolic imaging (DMI) has been demonstrated as a powerful technique for the imaging of metabolism in vivo. Here, we assess the metabolic flux of [6,6'-2 H2 ] fructose in cell cultures and in subcutaneous mouse models at 9.4 T. We compare these rates with the most widely used DMI probe, [6,6'-2 H2 ] glucose, exploring the possibility of developing 2 H fructose to overcome the limitations of glucose as a novel DMI probe for detecting liver tumors. Comparison of the in vitro metabolic rates implies their similar glycolytic metabolism in the TCA cycle due to comparable production rates of 2 H glutamate/glutamine (glx) for the two precursors, but overall higher glycolytic metabolism from 2 H glucose because of a higher production rate of 2 H lactate. In vivo kinetic studies suggest that HDO can serve as a robust reporter for the consumption of the precursors in liver tumors. As fructose is predominantly metabolized in the liver, deuterated water (HDO) produced from 2 H fructose is probably less contaminated from whole-body metabolism in comparison with glucose. Moreover, in studies of the normal liver, 2 H fructose is readily converted to 2 H glx, enabling the characterization of 2 H fructose kinetics. This overcomes a major limitation of previous 2 H glucose studies in the liver, which were unable to confidently discern metabolic flux due to overlapped signals of 2 H glucose and its metabolic product, 2 H glycogen. This suggests a unique role for 2 H fructose metabolism in HCC and the normal liver, making it a useful approach for assessing liver-related diseases and the progression to oncogenesis.

Comparative analysis of the gut microbiota of wild adult rats from nine district areas in Hainan, China.

BACKGROUND: Wild rats have the potential to hold zoonotic infectious agents that can spread to humans and cause disease. AIM: To better understand the composition of gut bacterial communities in rats is essential for preventing and treating such diseases. As a tropical island located in the south of China, Hainan province has abundant rat species. Here, we examined the gut bacterial composition in wild adult rats from Hainan province. METHODS: Fresh fecal samples were collected from 162 wild adult rats, including three species (Rattus norvegicus, Leopoldamys edwardsi, and Rattus losea), from nine regions of Hainan province between 2017-2018. RESULTS: We analyzed the composition of gut microbiota using the 16S rRNA gene amplicon sequencing. We identified 4903 bacterial operational taxonomic units (30 phyla, 175 families, and 498 genera), which vary between samples of different rat species in various habitats at various times of the year. In general, Firmicutes were the most abundant phyla, followed by Bacteroidetes (15.55%), Proteobacteria (6.13%), and Actinobacteria (4.02%). The genus Lactobacillus (20.08%), unidentified_Clostridiales (5.16%), Romboutsia (4.33%), unidentified_Ruminococcaceae (3.83%), Bacteroides (3.66%), Helicobacter (2.40%) and Streptococcus (2.37%) were dominant. CONCLUSION: The composition and abundance of the gut microbial communities varied between rat species and locations. This work provides fundamental information to identify microbial communities useful for disease control in Hainan province.

Gegen Qinlian Decoction treatment of asymptomatic hyperuricemia by targeting circadian immune function.

BACKGROUND: The Gegen Qinlian Decoction (GGQLD) is a renowned traditional Chinese medicinal formula that has been used for centuries to effectively treat asymptomatic Hyperuricemia (HUA). This study aims to investigate the underlying mechanism of GGQLD's therapeutic effects on HUA. METHODS: The study enrolled a total of 25 healthy participants and 32 middle-aged and elderly individuals with asymptomatic HUA. All asymptomatic HUA participants were treated with GGQLD. Venous blood samples were collected from all participants to isolate peripheral blood mononuclear cells (PBMCs), which were then analyzed for biological profiles using flow cytometry. Network pharmacology analysis was utilized to identify the potential pathways involved in the therapeutic effects of GGQLD. Transcriptomic patterns of cultured proximal tubule epithelial cells (PTECs) were evaluated via bulk RNA-seq, and critical differentially expressed genes (DEGs) were identified and verified through ELISA. Molecular docking and molecular dynamics (MD) simulation were employed to investigate the potential compounds in GGQLD that may be involved in treating HUA. RESULTS: Network pharmacology analysis revealed that immune-related pathways might be involved in the therapeutic mechanism of GGQLD. RNA-seq analysis confirmed the involvement of innate lymphoid cell (ILC) development-related genes and clock genes. Polychromatic flow cytometric analysis demonstrated that GGQLD treatment reduced the proportion of ILC3s in total ILCs in asymptomatic HUA patients. ELISA results showed that GGQLD treatment reduced the levels of activating factors, such as ILC3-IL-18 and IL-1ß, in the plasma of HUA patients. GGQLD was also found to regulate circadian clock gene expression in PBMCs to treat asymptomatic HUA. Furthermore, the interaction between 40 compounds in GGQLD and HDAC3 (Histone Deacetylase 3), NLRP3 (NOD-like receptor protein 3), RORA (RAR-related orphan receptor A), and REV-ERBα (nuclear receptor subfamily 1) revealed that GGQLD may regulate ILCs and clock genes to treat asymptomatic HUA. CONCLUSIONS: The regulation of circadian clock gene expression and the proportion of ILC cells may be involved in the therapeutic effects of GGQLD on asymptomatic HUA patients.

Atomic Resolution Cryogenic 4D-STEM Imaging via Robust Distortion Correction.

Cryogenic four-dimensional scanning transmission electron microscopy (4D-STEM) imaging is a useful technique for studying quantum materials and their interfaces by simultaneously probing charge, lattice, spin, and chemistry on the atomic scale with the sample held at temperatures ranging from room to cryogenic. However, its applications are currently limited by the instabilities of cryo-stages and electronics. To overcome this challenge, we develop an algorithm to effectively correct the complex distortions present in atomic resolution cryogenic 4D-STEM data sets. This method uses nonrigid registration to identify localized distortions in a 4D-STEM and relate them to an undistorted experimental STEM image, followed by a series of affine transformations for distortion corrections. This method allows a minimum loss of information in both reciprocal and real spaces, enabling the reconstruction of sample information from 4D-STEM data sets. This method is computationally cheap, fast, and applicable for on-the-fly data analysis in future in situ cryogenic 4D-STEM experiments.

Intracorporeal Anastomosis Versus Extracorporeal Anastomosis in Laparoscopic Right Colectomy: An Observational Cohort Study.

BACKGROUND: Current studies did not draw definitive conclusions on comparison of intracorporeal anastomosis (ICA) with extracorporeal anastomosis (ECA) in laparoscopic right colectomy. Whether the intraperitoneal contamination induced by ICA can result in higher risk of postoperative abdominal infection remains unclear. This study was aimed to compare the short-term outcomes, especially the risk of abdominal infection after ICA versus ECA. METHODS: This was an observational cohort study as a secondary analysis of a randomized controlled trial (RCT)-RELARC trial (NCT02619942). The patients enrolled in the RELARC trial were diagnosed with primary colon adenocarcinoma without distant metastasis and underwent radical laparoscopic right colectomy between Jan 2016 and Dec 2019. In our study the patients who converted to open surgery in RELARC trial were excluded. The short-term outcomes were compared between ICA and ECA. The primary endpoint was abdominal infection. The inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) was used for adjusting the potential confounders. RESULTS: This study enrolled 975 patients with 119 patients undergoing ICA and 856 patients undergoing ECA. The incidence of abdominal infection was higher in ICA group (9.2% versus 1.5%, RR from IPTW = 5.7 (95%CI: 2.6-12.6), P < 0.001) as well as the incidence of wound infection (14.3% vs 3.3%, RR from IPTW = 5.0 (95%CI: 2.9-8.6), P < 0.001). ICA was associated with higher incidence of Clavien-Dindo (CD) grade I and II complications (CD-I: 15.1% versus 6.8%, RR from IPTW = 2.4 (95%CI: 1.5-3.9), P < 0.001; CD-II: 26.9% versus 8.2%, RR from IPTW = 3.6 (95%CI: 2.5-5.1), P < 0.001) but similar incidence of CD-III ~ IV complications compared to ECA (3.4% vs 2.1%, RR from IPTW = 1.2 (95%CI: 0.4-4.0), P = 0.73). In ICA group, choosing another incision rather than lengthening main port site decreased the incidence of wound infection although without statistical significance (17.3% (14/81) versus 7.9% (3/38), crude RR = 2.2 (95%CI: 0.7-7.2), P = 0.17). CONCLUSION: ICA is likely to be associated with higher risk of abdominal infection and CD-I ~ II complications.

Comparison of safety of loop ileostomy and loop transverse colostomy for low-lying rectal cancer patients undergoing anterior resection: A retrospective, single institution, propensity score-matched study.

INTRODUCTION: This study was to compare the prevalence of stoma-related complications and stoma reversal perioperative complications of patients with low-lying rectal cancer who received preventative loop ileostomy and those who underwent loop transverse colostomy. METHODS: This retrospective single-center study analyzed the clinicopathologic and surgical data of 288 patients with pathologically proven primary rectal cancer who underwent anterior resection with either preventative loop ileostomy (n = 82) or loop transverse colostomy. To achieve comparability of a propensity score matching method was used to match patients from each group in a 1:2 ratio. Determinants of stoma-related complications were analyzed by multivariate logistic regression analysis. RESULTS: Forty-nine (74.3%) patients in the loop ileostomy group experienced stoma-related complications versus 48.7% in the loop transverse colostomy group (P < 0.01). Irritant dermatitis was the most frequent complication in both groups. The loop ileostomy group had a significantly higher rate (24.24%) of stoma reversal perioperative complications than the loop transverse colostomy group. Multivariate logistic regression analysis showed that ileostomy versus loop transverse colostomy was a significant independent risk for stoma-related complications and stoma reversal perioperative complications. Furthermore, by Clavien-Dindo classification, patients receiving loop ileostomy had an overall higher rate of complications and stoma reversal perioperative complications versus those undergoing loop transverse colostomy (P < 0.01). The rate of grade II complications was significantly higher in the loop ileostomy group (43.9%) than that of loop transverse colostomy group (13.5%, P < 0.01), whereas the rate of grade I, and grade IIIa and IIIb complications and stoma reversal perioperative complications was comparable between the two groups. CONCLUSION: The study has demonstrated that loop transverse colostomy is associated with significantly lower rates of stoma-related complications and stoma reversal perioperative complications compared to loop transverse colostomy.

Conversion immunotherapy for deficient mismatch repair locally unresectable colon cancer: A case report.

BACKGROUND: Owing to the special features of biologics, deficient mismatch repair (dMMR) in patients with colon cancer has achieved little treatment efficacy from chemoradiotherapy. Immunotherapy has shown promising results for the treatment of colon cancer. The high response rate observed suggests a great option for patients presenting with unresectable tumors, as it allows for better oncological resection. Here, we aimed to highlight the significant effects of immunotherapy on dMMR in colon cancer. CASE SUMMARY: A 54-year-old man diagnosed with locally unresectable dMMR colon cancer received preoperative immunotherapy (three cycles of pembrolizumab) and achieved a pathological complete response after surgery. CONCLUSION: Immunotherapy can be used as a conversion treatment for locally unresectable colon cancer with dMMR.

Risk Factors for Pulmonary Metastasis in Differentiated Thyroid Carcinoma Patients and the Significance of Changes in Matrix Metalloproteinase 13 and microRNA-142 Levels.

This work aims to explore the risk factors of lung metastasis (LM) in differentiated thyroid cancer (DTC) (LM-DTC) and the effect of treatment and to detect the relationship between LM-DTC and the levels of matrix metalloproteinase-13 (MMP-13) and micro ribonucleic acid (RNA)-142 (miR-142) in peripheral blood. The data of 420 patients with DTC who are admitted from March 2020 to December 2021 are collected and divided into a non-metastasis group (non-LM group) of 400 cases and metastasis group (LM group) of 20 cases according whether the mung metastasis is found. In addition, risk factors of LM-DTC are analysed and compared. The results of multivariate logistic analysis show that age, disease course, and imaging timing are independent influencing factors of the radionuclide treatment effect. Follicular carcinoma, abnormal expressions of MMP-13, and miR-142 can increase the risk of LM-DTC. MMP-13 and miR-142 can be undertaken as auxiliary diagnostic biological indicators.

MG53 inhibits cellular proliferation and tumor progression in colorectal carcinoma.

Cancer is the second leading cause of mortality after cardiovascular diseases in the United States. Chemotherapy is widely used to treat cancers. Since the development of drug resistance is a major contributor towards the failure of chemotherapeutic regimens, efforts have been made to develop novel inhibitors that can combat drug resistance and sensitize cancer cells to chemotherapy. Here we investigated the anti-cancer effects of MG53, a TRIM-family protein known for its membrane repair functions. We found that rhMG53 reduced cellular proliferation of both parental and ABCB1 overexpressing colorectal carcinoma cells. Exogenous rhMG53 protein entered SW620 and SW620/AD300 cells without altering the expression of ABCB1 protein. In a mouse SW620/AD300 xenograft model, the combination of rhMG53 and doxorubicin treatment significantly inhibited tumor growth without any apparent weight loss or hematological toxicity in the animals. Our data show that MG53 has anti-proliferative function on colorectal carcinoma, regardless of their nature to drug-resistance. This is important as it supports the broader value for rhMG53 as a potential adjuvant therapeutic to treat cancers even when drug-resistance develops.

Knockdown circTRIM28 enhances tamoxifen sensitivity via the miR-409-3p/HMGA2 axis in breast cancer.

BACKGROUND: Tamoxifen (TAM) is a frequently-used treatment for breast cancer (BC). But the TAM resistance seriously affects the patient therapeutic effect. Previous research indicated that circular RNAs (circRNAs) might participate in the regulatory processes of BC. Here, we discovered the parts of circular RNA tripartite motif-containing 28 (circTRIM28) in BC. METHODS: CircTRIM28, microRNA-409-3p (miR-409-3p), and high mobility group AT-hook 2 (HMGA2) levels were perceived by qRT-PCR and western blot. Moreover, the biological functions of the cells were examined. Furthermore, dual-luciferase report was employed to reconnoiter the targeted relationship between miR-409-3p and circTRIM28 or HMGA2. RESULTS: CircTRIM28 and HMGA2 were augmented, and the miR-409-3p was repressed in BC. Silencing circTRIM28 enhanced tamoxifen sensitivity and cell apoptosis, whereas hampered cell development in BC cells. In mechanism, circTRIM28 could sponge miR-409-3p to increase HMGA2. In addition, silencing circTRIM28 impeded tumor growth. CONCLUSION: CircTRIM28 facilitated the BC via miR-409-3p/HMGA2.