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The macrovascular complications of diabetes cause high mortality and disability in patients with type 2 diabetes mellitus (T2DM). The inflammatory response of vascular smooth muscle cell (VSMC) runs through its pathophysiological process. Salvianolic acid B (Sal B) exhibits beneficial effects on the cardiovascular system. However, its role and mechanism in diabetic vascular inflammatory response remain unclear. In this study, we found that Sal B reduced vascular inflammation in diabetic mice and high glucose- (HG-) induced VSMC inflammation. Subsequently, we found that Sal B reduced HG-induced VSMC inflammation by downregulating FOXO1. Furthermore, miR-486a-5p expression was obviously reduced in HG-treated VSMC. Sal B attenuated HG-induced VSMC inflammation by upregulating miR-486a-5p. Loss- and gain-of-function experiments had proven that the transfection of the miR-486a-5p mimic inhibited HG-induced VSMC inflammation whereas that of the miR-486a-5p inhibitor promoted HG-induced VSMC inflammation, thereby leading to the amelioration of vascular inflammation in the diabetic mice. Furthermore, studies had shown that miR-486a-5p inhibited FOXO1 expression by directly targeting its 3'-UTR. In conclusion, Sal B alleviates the inflammatory response of VSMC by upregulating miR-486a-5p and aggravating its inhibition of FOXO1 expression. Sal B exerts a significant anti-inflammatory effect in HG-induced VSMC inflammation by modulating the miR-486a-5p/FOXO1 axis., Competing Interests: The authors have no conflict of interest to disclose., (Copyright © 2024 Man-Li Zhang et al.)

Rationale: Neointimal hyperplasia caused by dedifferentiation and proliferation of venous smooth muscle cells (SMCs) is the major challenge for restenosis after coronary artery bypass graft. Herein, we investigated the role of Lamtor1 in neointimal formation and the regulatory mechanism of non-coding RNA underlying this process. Methods: Using a "cuff" model, veins were grafted into arterial system and Lamtor1 expression which was correlated with the activation of mTORC1 signaling and dedifferentiation of SMCs, were measured by Western blot. Whole transcriptome deep sequencing (RNA-seq) of the grafted veins combined with bioinformatic analysis identified highly conserved circSlc8a1 and its interaction with miR-20a-5p, which may target Lamtor1 . CircSlc8a1 was biochemically characterized by Sanger sequencing and resistant to RNase R digestion. The cytoplasmic location of circSlc8a1 was shown by fluorescence in situ hybridization (FISH). RNA pull-down, luciferase assays and RNA immunoprecipitation (RIP) with Ago2 assays were used to identify the interaction circSlc8a1 with miR-20a-5p. Furthermore, arterial mechanical stretch (10% elongation) was applied in vitro . Results: In vivo , Lamtor1 was significantly enhanced in grafted vein and activated mTORC1 signaling to promote dedifferentiation of SMCs. Arterial mechanical stretch (10% elongation) induced circSlc8a1 expression and positively regulated Lamtor1, activated mTORC1 and promoted SMC dedifferentiation and proliferation. Local injection of circSlc8a1 siRNA or SMC-specific Lamtor1 knockout mice prevented neointimal hyperplasia in vein grafts in vivo . Conclusions: Our study reveals a novel mechanobiological mechanism underlying the dedifferentiation and proliferation of venous SMCs in neointimal hyperplasia. CircSlc81/miR-20a-5p/Lamtor1 axis induced by arterial cyclic stretch may be a potential clinical target that attenuates neointimal hyperplasia in grafted vessels., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Excessive release of cytokines such as IL-1 β and other inflammatory mediators synthesized and secreted by macrophages is the fundamental link of uncontrolled inflammatory response in sepsis. 17 β -Estradiol (E2) plays anti-inflammatory and vascular protective effects by regulating leukocyte infiltration and the expression of chemokines or cytokines induced by injury. However, the role of E2 in the inflammatory response of macrophages in sepsis and its mechanism are still not fully understood. In the present study, we show that E2 alleviates vascular inflammation in sepsis mice induced by cecal ligation puncture (CLP). E2 significantly decreases RAW 264.7 cell inflammation response by downregulating the expression of NLRP3. Furthermore, we found that miR-29a-5p was significantly downregulated in LPS-treated macrophages. Treating RAW 264.7 cells with E2 markedly upregulated the miR-29a-5p expression level. More importantly, we demonstrated that miR-29a-5p repressed NLRP3 expression by directly targeting its 3'-UTR. Loss- and gain-of-function experiments revealed that transfection of the miR-29a-5p mimic abrogates LPS-induced macrophage inflammation. Moreover, depletion of miR-29a-5p by its inhibitor largely promotes LPS-induced macrophage inflammation. In summary, miR-29a-5p upregulation induced by E2 alleviated RAW 264.7 cell inflammation response by aggravating miR-29a-5p repression of NLRP3 expression. E2 exerts significant anti-inflammatory efficacy in macrophages by regulating the miR-29a-5p/NLRP3 axis. Targeting miR-29a-5p may be a novel therapeutic strategy to suppress sepsis-induced vascular inflammation., Competing Interests: The authors have no conflict of interest to disclose., (Copyright © 2021 Man-li Zhang et al.)

Objectives: This study aims to construct endogenous exosomes abundantly loaded with miR-1 and investigate the role of exosome-mediated microRNA-1 (miR-1) delivery on CAL-27 cell proliferation., Methods: Exosomes secreted by miR-1-overexpressing HEK293 cells (miR1-EXO) were purified via ultracentrifugation and subjected to transmission electron microscopy, nanoparticle analysis, Western blot analysis, and quantitative polymerase chain reaction (qPCR). CAL-27 cells were cocultured with exosomes secreted by HEK293 cells (CON-EXO) and miR1-EXO and equivalent phosphate buffer saline. The intracellular transport of exosomes was measured by using immunofluorescence, the expression of miR-1 and its target gene MET were investigated via qPCR, CAL-27 cell proliferation was measured through MTT assay, and cell cycle state was determined by applying flow cytometry., Results: Electron microscopy revealed that miR1-EXO and CON-EXO were spherical or cup-shaped with an average diameter of approximately 110 nm. The well-known exosome markers CD9, Tsg101, and Alix were enriched. The expression of miR-1 in miR1-EXO was higher than that in CON-EXO (285.80±14.33 vs 1.00±0.06, P< 0.000 1). After coculture with CAL-27 cells, miR1-EXO was internalized and unloaded miR-1 into CAL-27 cells. After coculture with miR1-EXO, the expression of miR-1 in CAL-27 cells was upregulated, whereas that of MET, the target gene of miR-1, was suppressed and the proliferation of CAL-27 cells was inhibited significantly. Normal oral keratinocyte cell proliferation was negligibly affected after coculture with miR1-EXO., Conclusions: Exosomes secreted from miR1-EXO cells could load abundant miR-1. Exosomal miR-1 delivered into CAL-27 cells by using miR1-EXO suppressed the expression of MET mRNA and inhibited cell proliferation.

Objective: The aim of this study was to explore the regulatory effect of micro ribonucleic acid (miR)-20a on nuclear factor-κB (NF-кB) in liver cancer Huh-7 cells, and to elucidate its influence on the chemosensitivity of Huh-7 cells., Materials and Methods: Huh-7 cells with overexpression of miR-20a or knockout of miR-20a were first constructed. Quantitative polymerase chain reaction (qPCR) was adopted to detect the expression level of miR-20a in each group of cells. The sensitivity of cells to cisplatin and doxorubicin in each group was measured using methyl thiazolyl tetrazolium (MTT) assay, and the 50% inhibitory concentration (IC50) was calculated. Hoechst 33258 staining was performed to detect the apoptosis of cells in each group. Furthermore, the expression levels of apoptosis-associated proteins and the NF-кB signaling pathway-related proteins in each group of cells were determined via Western blotting., Results: The expression level of miR-20a in blank control group was considerably higher than that in knockout group (p<0.01). Meanwhile, cells in overexpression group exhibited a notably higher expression level of miR-20a than blank control group (p<0.01). Cells in knockout group had dramatically enhanced sensitivity to doxorubicin and cisplatin (p<0.01), with a prominently decreased IC50 value (p<0.01). However, cells in overexpression group exhibited remarkably weakened sensitivity (p<0.01) and increased IC50 value (p<0.01). After treatment with doxorubicin and cisplatin, the apoptosis level of cells rose substantially in knockout group (p<0.01), whereas declined significantly in overexpression group (p<0.01). Moreover, knockout group exhibited a notably elevated expression level of Caspase-3 (p<0.01), and a considerably decreased ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (Bax) (p<0.01). The expression level of Caspase-3 declined remarkably (p<0.01), however, the ratio of Bcl2/Bax increased substantially (p<0.01) in overexpression group. The expression level of NF-кB inhibitor beta (NF-кBIB) was markedly up-regulated (p<0.01), while the expression levels of Livin and Survivin declined remarkably (p<0.01) in knockout group. Furthermore, overexpression group had a considerably decreased expression level of NF-кBIB (p<0.01), but notably increased expression levels of Livin and Survivin (p<0.01)., Conclusions: MiR-20a up-regulates the expressions of the downstream proteins Livin and Survivin, decreases the expressions of apoptosis-associated proteins, weakens the sensitivity of cells to chemotherapy drugs and lowers the apoptosis level of cells by activating the NF-кB signaling pathway in liver cancer Huh-7 cells.

MicroRNA (miR)-103a-3p has been shown to be involved in the development and progression of several types of cancer. However, the role of miR-103a-3p in thyroid cancer remains unclear. This study investigated the effects of miR-103a-3p on the biological characteristics of thyroid cancer cells and related mechanisms. In the present study, we found that the expression of miR-103a-3p was increased in thyroid cancer tissues compared to that in non-cancerous tissues. Additionally, the expression of miR-103a-3p in thyroid cancer cell lines (TPC-1, SW579, BHT101, K1) was markedly higher than that in the human thyroid cell line (Nthy-ori3-1). Silencing of miR-103a-3p obviously inhibited proliferation, migration, and invasion and promoted apoptosis of BHT101 cells. miR-103a-3p upregulation promoted the proliferation, migration, and invasion and inhibited apoptosis of K1 cells. Mechanistically, LATS1 was identified as a functional target of miR-103a-3p, and miR-103a-3p negatively regulated LATS1 expression. miR-103a-3p knockdown (or upregulation) partially reversed the effects of LATS1 knockdown (or overexpression) on proliferation, apoptosis, migration, and invasion of thyroid cancer cells. LATS1 knockdown inhibited the phosphorylation of YAP in BHT101 cells and promoted the nuclear translocation of YAP. Whereas, miR-103a-3p downregulation reversed the inhibitory effect of LATS1 knockdown on the Hippo signaling pathway. Moreover, overexpression of LATS1 induced YAP phosphorylation in K1 cells and inhibits nuclear translocation of YAP, and the upregulation of miR-103a-3p reversed this effect. The knockdown of miR-103a-3p inhibited tumor growth and progression in vivo. Taken together, knockdown of miR-103a-3p inhibits proliferation, migration, and invasion and promotes apoptosis of thyroid cancer cells through the Hippo signaling pathway by upregulating LATS1.

As important modulators in multiple physiological processes, microRNAs (miRNAs) have been reported in various malignant tumors, including breast cancer. The current study investigated the function of a new tumor suppressor microRNA, miR-488, and its molecular mechanism of metastasis in breast cancers. CCK8 and transwell assays revealed that the upregulated miR-488 level significantly inhibited the proliferation and migration of breast cancer cells. As a potential downstream gene, the mRNA and protein level of FSCN1 was suppressed by increased miR-488 and vice versa. Luciferase assay showed that miR-488 directly bind to the 3'UTR of FSCN1 and suppressed the translation process of FSCN1. The promoter region of miR-488 was directly bound by Notch3 and promoted the expression of miR-488 transcriptionally. Immunohistochemistry results revealed that in patients with breast cancer, the expression of Notch3 and were negatively correlated with the FSCN1 levels significantly. Therefore, the current finding predicted miR-488 as a tumor suppressor molecule in breast cancer, and demonstrated that Notch3/miR-488/FSCN1 axis is established and involved in regulating the metastasis of breast cancers, providing novel therapeutic targets for patients with breast cancers.

Long non-coding RNAs (lncRNAs) have been demonstrated to act as essential regulators in the growth and progression of neuroblastoma. In the present research, the high expression of lncRNA small nucleolar RNA host gene 4 (SNHG4) in neuroblastoma was tested via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and then the function of SNHG4 was explored and verified by CCK-8 assay, EdU assay, cell cycle assay, cell apoptosis test, wound healing test and invasion test in neuroblastoma cell lines. It was discovered that lncRNA SNHG4 exhibited high expression in neuroblastoma tissues and cell lines, and the expression of SNHG4 was associated with the survival of neuroblastoma patients. Additionally, SNHG4 decrement markedly repressed neuroblastoma cells to proliferate and stimulate their apoptosis in vivo and in vitro. Moreover, SNHG4 decrement impeded the abilities of SH-SY5Y and IMR-32 cells to migrate and invade as well as epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG4 acted as a competing endogenous RNA to sponge miR-377-3p, which was downregulated in neuroblastomas and inhibited cell proliferation and invasion. The findings manifested that SNHG4 was inversely associated with miR-377-3p expression in neuroblastoma cases. Collectively, we revealed the functions of SNHG4 and miR-377-3p in neuroblastoma.

Objective: To explore the mechanism of miR-223-3p regulating the occurrence and development of liver cancer cells by targeting FAT1 gene. Methods: Bioinformatics analysis was used to analyze the differentially expressed genes in liver cancer tissue chips. Forty-eight cases of liver cancer tissues and corresponding adjacent tissues were selected, and qRT-PCR was used to detect the expression of miR-223-3p and FAT1mRNA in tissues. Wound healing assay was used to detect the migration ability of liver cancer cells. Transwell assay was used to detect cells invasion ability. Dual-luciferase assay was used to detect the targeting relationship between miR-223-3p and FAT1. Western blot was used to detect the protein expression of EMT-related markers, E-cadherin and Vimentin. Results: FAT1 was highly expressed in liver cancer tissues and cells, while miR-223-3p was lowly expressed. Silencing FAT1 could inhibite the proliferation, migration, invasion and EMT of liver cancer cells. miR-223-3p targeted down-regulated the expression of FAT1, and inhibited the proliferation, migration, invasion and EMT of liver cancer cells by targeting FAT1. Conclusion: miR-223-3p regulates the occurrence and development of liver cancer cells by targeted down-regulating the expression of FAT1.

p53, circRNAs and miRNAs are important components of the regulatory network that activates the EMT program in cancer metastasis. In prostate cancer (PCa), however, it has not been investigated whether and how p53 regulates EMT by circRNAs and miRNAs. Here we show that a Amotl1-derived circRNA, termed circAMOTL1L, is downregulated in human PCa, and that decreased circAMOTL1L facilitates PCa cell migration and invasion through downregulating E-cadherin and upregulating vimentin, thus leading to EMT and PCa progression. Mechanistically, we demonstrate that circAMOTL1L serves as a sponge for binding miR-193a-5p in PCa cells, relieving miR-193a-5p repression of Pcdha gene cluster (a subset of the cadherin superfamily members). Accordingly, dysregulation of the circAMOTL1L-miR-193a-5p-Pcdha8 regulatory pathway mediated by circAMOTL1L downregulation contributes to PCa growth in vivo. Further, we show that RBM25 binds directly to circAMOTL1L and induces its biogenesis, whereas p53 regulates EMT via direct activation of RBM25 gene. These findings have linked p53/RBM25-mediated circAMOTL1L-miR-193a-5p-Pcdha regulatory axis to EMT in metastatic progression of PCa. Targeting this newly identified regulatory axis provides a potential therapeutic strategy for aggressive PCa.

Retained fetal membranes (RFM) of cows is an important reproductive disturbance, and is related to miRNA-185. Stromal interaction molecule 1 (STIM1), a potential target gene of miRNA-185, could influence placenta release via regulating Ca 2+ concentration intracellular. The aim of this study was to explore the mechanism of RFM by investigating the regulatory relationship between miRNA-185 and STIM1 in primary uterine caruncel epithelial (UCE) cells. Serum samples of healthy Holstein dairy cows (n = 20) and RFM cows (n = 12), with a similar age, parity, weight, and milk yield, were collected to detect Ca 2+ concentration at prepartum 1-5 d and postpartum 6, 12 and 24 h. Caruncle tissues were collected from healthy (n = 6) and RFM cows (n = 6) at 12 h after calving. Quantitative polymerase chain reaction (Q-PCR) and western blotting (WB) were performed to detect the mRNA and protein levels of STIM1, respectively. UCE cells were cultured by the explant culture method, further purified, and subsequently treated with PmirGLO-STIM1-Mut + miRNA-185 mimics and mirGLO-STIM1-Mut + miRNA-185 NC. Q-PCR and WB were performed to detect mRNA and protein levels of STIM1 with treated miRNA-185 mimics. Serum levels of Ca 2+ from RFM cows were abnormally decreased at prepartum 1 d and postpartum 6, 12 and 24 h. Expression level of STIM1 was down-regulated in the caruncle tissue of RFM cows. The luciferase activity was decresed about 30.9% by miRNA-185 mimics (p < 0.01), and the mRNA and protein levels of STIM1 were downregulated miRNA-185-mimics. It was suggesting that miRNA-185 might play an important role in RFM through regulating the expression of STIM1., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Ulcerative colitis (UC) is an unexplained inflammatory disease in bowel. Some studies reported that microRNA-19b (miR-19b) was closely related to cell inflammatory response. We aimed to explore the molecular mechanism of miR-19b on lipopolysaccharide (LPS)-induced human intestinal cell inflammatory injury., Materials and Methods: Caco2 cells were treated with 10 ng/ml LPS to induce inflammatory injury. The expression of miR-19b and runt-related transcription factor 3 (Runx3) was changed in Caco2 cells by cell transfection. Then, the viability, apoptosis and pro-inflammatory factors expressions of transfected cells were assessed using trypan blue exclusion assay, flow cytometry, qRT-PCR, Western blotting and enzyme-linked immunosorbent assay (ELISA), respectively, after LPS treatment. At last, the expressions of key factors involved in nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase/protein kinase 3 (PI3K/AKT) pathways were evaluated using Western blotting., Results: LPS significantly induced Caco2 cell inflammatory injury, down-regulated miR-19b expression and activated NF-κB and PI3K/AKT pathways. Suppression of miR-19b enhanced the LPS-induced Caco2 cell inflammatory injury, as well as NF-κB and PI3K/AKT pathways activation. Overexpression of miR-19b had opposite effects. In addition, miR-19b regulated the expression of Runx3 in Caco2 cells. Overexpression of Runx3 reversed the miR-19b knockdown-induced Caco2 cell viability inhibition, apoptosis enhancement, inflammatory factors expressions and NF-κB and PI3K/AKT signaling pathways activation., Conclusions: Our study demonstrated that miR-19b alleviated LPS-induced Caco2 cell inflammatory injury via up-regulation of Runx3 and deactivation of NF-κB and PI3K/AKT signaling pathways.

Retention of fetal membranes (RFM) of cows is an important reproductive disturbance, and is related to miRNAs. Vascular endothelial growth factor (VEGF)A, regulated by miRNA-185, can activate arachidonic acid (ARA) release via the VEGFA signaling pathway, which influences RFM. The aim of this study was to explore the pathogenic mechanism of RFM by investigating the regulatory relationship between miRNA-185 and the VEGFA signaling pathway. Serum samples of healthy Holstein dairy cows (n = 20) and RFM cows (n = 12), with a similar age, parity, weight, and milk yield, were collected to detect VEGFA and ARA concentrations at 6, 12, and 24 h after calving. Caruncle tissues were collected from healthy (n = 6) and RFM cows (n = 6) at 12 h after calving. Quantitative polymerase chain reaction (qPCR) and western blotting (WB) were performed to detect the mRNA and proteins levels, respectively, of genes involved in the VEGFA signaling pathway. Uterine caruncle epithelial (UCE) cells were cultured by the explant culture method, further purified, and subsequently treated with miRNA-185 mimics, miRNA-185 mimics + MEK inhibitor, or left untreated as a control for detection of the mRNA and protein levels of genes involved in the VEGFA signaling pathway. The cellular supernatant was collected for measurement of ARA levels at 12, 24 and 48 h after treatment. Serum levels of VEGFA and ARA from RFM cows were abnormally increased at 12 h after calving, as compared to those in healthy dairy cows. Expression levels of most of the investigated genes (VEGFA, PLC, PRK, RAF, MEK, MAPK, and PLA) were down-regulated in the caruncle tissue of RFM cows. However, P-p44/42 MAPK was up-regulated in the caruncle tissues of cows with RFM (p < .01). In UCE cells treated with the miRNA-185 mimics, expression of VEGFA, PLC, RAF, MEK, MAPK and PLA was significantly down-regulated, while that of P-p44/42 MAPK was significantly up-regulated. Expression of genes involved in the VEGFA signaling pathway was similar to that in the in vivo assay. In UCE cells treated with the miRNA-185 mimics + MEK inhibitors, expression of VEGFA, PLC, RAF, MEK, MAPK and P-p44/42 MAPK was significantly down-regulated, while that of PLA was significantly up-regulated. Meanwhile, the release of ARA was increased (p < .01). These results demonstrate that miRNA-185 can regulate the VEGFA signaling pathway, especially via abnormal expression of P-p44/42 MAPK, which influences the release of the fetal placenta after calving., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Docetaxel-based chemotherapy failure in advanced prostate carcinoma has partly been attributed to the resistance of prostate cancer (PC) cells to docetaxel-induced apoptosis. Hence, there is an urgent need to identify mechanisms of docetaxel chemoresistance and to develop new combination therapies., Methods: miR-193a-5p level was evaluated by qPCR in prostate tissues and cell lines, and its expression in the tissues was also examined by in situ hybridization. PC cell line (PC3 cell) was transfected with miR-193a-5p mimic or its inhibitor, and then cell apoptosis and the expression of its downstream genes Bach2 and HO-1 were detected by TUNEL staining and Western blotting. Luciferase reporter assay was used to detect the effect of miR-193a-5p and Bach2 on HO-1 expression. Xenograft animal model was used to test the effect of miR-193a-5p and docetaxel on PC3 xenograft growth., Results: miR-193a-5p was upregulated in PC tissues and PC cell lines, with significant suppression of PC3 cell apoptosis induced by oxidative stress. Mechanistically, miR-193a-5p suppressed the expression of Bach2, a repressor of the HO-1 gene, by directly targeting the Bach2 mRNA 3'-UTR. Docetaxel treatment modestly decreased Bach2 expression and increased HO-1 level in PC3 cells, whereas a modest increase of HO-1 facilitated docetaxel-induced apoptosis. Notably, docetaxel-induced miR-193a-5p upregulation, which in turn inhibits Bach2 expression and thus relieves Bach2 repression of HO-1 expression, partly counteracted docetaxel-induced apoptosis, as evidenced by the increased Bcl-2 and decreased Bax expression. Accordingly, silencing of miR-193a-5p enhanced sensitization of PC3 cells to docetaxel-induced apoptosis. Finally, depletion of miR-193a-5p significantly reduced PC xenograft growth in vivo., Conclusions: Silencing of miR-193a-5p or blockade of the miR-193a-5p-Bach2-HO-1 pathway may be a novel therapeutic approach for castration-resistant PC.

Rationale: Neuregulin-1 (NRG-1) includes an extracellular epidermal growth factor-like domain and an intracellular domain (NRG-1-ICD). In response to transforming growth factor-β1, its cleavage by proteolytic enzymes releases a bioactive fragment, which suppresses the vascular smooth muscle cell (VSMC) proliferation by activating ErbB (erythroblastic leukemia viral oncogene homolog) receptor. However, NRG-1-ICD function in VSMCs remains unknown., Objective: Here, we characterize the function of NRG-1-ICD and underlying mechanisms in VSMCs., Methods and Results: Immunofluorescence staining, Western blotting, and quantitative real-time polymerase chain reaction showed that NRG-1 was expressed in rat, mouse, and human VSMCs and was upregulated and cleaved in response to transforming growth factor-β1. In the cytoplasm of HASMCs (human aortic smooth muscle cells), the NRG-1-ICD participated in filamentous actin formation by interacting with α-SMA (smooth muscle α-actin). In the nucleus, the Nrg-1-ICD induced circular ACTA2 (alpha-actin-2; circACTA2) formation by recruitment of the zinc-finger transcription factor IKZF1 (IKAROS family zinc finger 1) to the first intron of α-SMA gene. We further confirmed that circACTA2, acting as a sponge binding microRNA (miR)-548f-5p, interacted with miR-548f-5p targeting 3' untranslated region of α-SMA mRNA, which in turn relieves miR-548f-5p repression of the α-SMA expression and thus upregulates α-SMA expression, thereby facilitating stress fiber formation and cell contraction in HASMCs. Accordingly, in vivo studies demonstrated that the localization of the interaction of circACTA2 with miR-548f-5p is significantly decreased in human intimal hyperplastic arteries compared with normal arteries, implicating that dysregulation of circACTA2 and miR-548f-5p expression is involved in intimal hyperplasia., Conclusions: These results suggest that circACTA2 mediates NRG-1-ICD regulation of α-SMA expression in HASMCs via the NRG-1-ICD/circACTA2/miR-548f-5p axis. Our data provide a molecular basis for fine-tuning α-SMA expression and VSMC contraction by transcription factor, circular RNA, and microRNA., (© 2017 American Heart Association, Inc.)

MicroRNA expression is a research focus in studies of tumors. This article concentrates attention on potential links between tumors caused by mouse mammary tumor virus (MMTV) and human breast cancer, in order to provide theoretical basis for using mouse model to search for miRNA effects mediated by Wnt/beta-catenin signaling in human breast cancer. By analyzing interactions between miRNAs and the Wnt/beta-catenin signaling pathway in breast cancer, we hope to casts light on more biological functions of miRNAs in the process of tumor formation and growth and to explore their potential value in cancer diagnosis, prognosis and treatment. Our endeavor aimed at providing theoretical basis for finding safer, more effective methods for treatment of human breast cancer at the miRNA molecular level.

Rabies virus (RABV) is known to cause a fatal infection in many mammalian species, yet its pathogenesis remains poorly understood. This study was performed to analyze the microRNA (miRNA) expression profiles in RABV-infected primary neurons of mice. A total of 53 miRNAs were found to be differentially expressed in RABV-infected samples compared with mock samples in a time-dependent manner. Among them, the expression of ten miRNAs was validated by real-time RT-PCR. Potential target genes of differentially expressed miRNAs were predicted by TargetScan. Further bioinformatics analysis indicated that these predicted targets were overrepresented in neuronal function-related Gene Ontology (GO) terms and biological pathways. The results of this study suggest that RABV may cause neuronal dysfunction by regulating cellular miRNA expression.