Circular RNA ATP2C1 (has_circ_0005797) sponges miR-432/miR-335 to promote breast cancer progression through regulating CCND1 expression.

Breast cancer (BC) is the most frequently diagnosed malignancy in the world. Accumulating evidence has indicated that circular RNAs (circRNAs) play essential roles in BC. Here we investigated the biological functions of circATP2C as a competing endogenous RNA (ceRNA) in BC development. We found that circATP2C1 expression was upregulated in BC cells and tissues and was significantly associated with the poor overall survival in BC patients. CircATP2C1 is more resistant to RNase R exonuclease and Actinomycin D than is the linear mRNA of ATP2C1. CircATP2C1-knockdown inhibited the viability, colony proliferation and invasion abilities, while increasing the apoptosis rates of BC cells in vitro, as well as inhibiting tumor mass, size and weight in vivo. Upregulation of miR-432 and miR-335 inhibited CCND1 expression in BC cells. Both miR-432/miR-335 specifically bind to the 3'-UTR of circATP2C1 and CCND1 (CyclinD1). The inhibition of the aggression of BC cells by circATP2C1-knockdown was rescued by co-transfection of miR-432/miR-335 inhibitors. In conclusion, circATP2C1 promotes BC oncogenesis and metastasis by sponging miR-432/miR-335 to abolish the inhibition of the target gene, CCND1. This study suggests that circATP2C1 has implications for BC diagnosis and treatment.

Solitary fibrous tumor of the liver: a case report.

Hepatic solitary fibrous tumor (SFT) is a rare tumor originating from the mesenchyme. Here we report a new case of SFT in the liver and review the clinical presentation, radiological and operative findings, diagnosis, treatment, and outcome. The patient was a 59-year-old man who presented with progressive fatigue for 3 months and an abdominal mass for 3 days. On laboratory tests, no abnormality was detected except that abdominal ultrasonography revealed a 9.0 × 6.2 cm hypoechogenic mass in the left lobe of the liver. A computed tomographic scan confirmed a hypodense lesion in the left lobe of the liver. The patient underwent left hepatectomy. SFT was diagnosed on the basis of histopathological findings. The patient was free from all symptoms and had no signs of local recurrence after 24 months' follow up.

Integrated Analysis of Circular RNA-Associated ceRNA Network Reveals Potential circRNA Biomarkers in Human Breast Cancer.

Circular RNA (circRNA) is closely related to tumorigenesis and cancer progression. Yet, the roles of cancer-specific circRNAs in the circRNA-related ceRNA network of breast cancer (BRCA) remain unclear. The aim of this study was to construct a ceRNA network associated with circRNA and to explore new therapeutic and prognostic targets and biomarkers for breast cancer. We downloaded the circRNA expression profile of BRCA from Gene Expression Omnibus (GEO) microarray datasets and downloaded the miRNA and mRNA expression profiles of BRCA from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were identified, and a competitive endogenous RNA (ceRNA) regulatory network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Gene ontology and pathway enrichment analyses were performed on mRNAs regulated by circRNAs in ceRNA networks. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network were performed. A total of 72 DEcircRNAs, 158 DEmiRNAs, and 2762 DE mRNAs were identified. The constructed ceRNA network contains 60 circRNA-miRNA pairs and 140 miRNA-mRNA pairs, including 40 circRNAs, 30 miRNAs, and 100 mRNAs. Functional enrichment indicated that DEmRNAs regulated by DEcircRNAs in ceRNA networks were significantly enriched in the PI3K-Akt signaling pathway, microRNAs in cancer, and proteoglycans in cancer. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network showed that 13 mRNAs and 6 miRNAs were significantly associated with overall survival, and 48 miRNA-mRNA interaction pairs had a significant negative correlation. A PPI network was established, and 21 hub genes were determined from the network. This study provides an effective bioinformatics basis for further understanding of the molecular mechanisms and predictions of breast cancer. A better understanding of the circRNA-related ceRNA network in BRCA will help identify potential biomarkers for diagnosis and prognosis.

Mitofusin-2 is a novel direct target of p53.

The tumor suppressor p53 modulates transcription of a number of target genes involved in cell cycle arrest, apoptosis, DNA repair, and other important cellular responses. Mitofusin-2 (Mfn2) is a novel suppressor of cell proliferation that may also exert apoptotic effects via the mitochondrial apoptotic pathway. Through bioinformatics analysis, we identified a p53 binding site in the Mfn2 promoter. Consistent with this, we showed that the p53 protein binds the Mfn2 promoter directly both in vitro and in vivo. Additionally, we found that Mfn2 mRNA and protein levels are up-regulated in a p53-dependent manner. Furthermore, luciferase assays revealed that the activity of the wild-type Mfn2 promoter, but not a mutated version of the promoter, was up-regulated by p53. These results indicate that Mfn2 is a novel p53-inducible target gene, which provides insight into the regulation of Mfn2 and its associated activities in the inhibition of cell proliferation, promotion of apoptosis, and modulation of tumor suppression.

Interactions Between lncRNA TUG1 and miR-9-5p Modulate the Resistance of Breast Cancer Cells to Doxorubicin by Regulating eIF5A2.

PURPOSE: Breast cancer (BC) is one of the leading causes of cancer-related deaths. Chemoresistance of BC remains a major unmet clinical obstacle. TUG1 (taurine-upregulated gene 1), a long noncoding RNA (lncRNA), and microRNAs (miRNA) are implicated in therapeutic resistance. However, the interactions between TUG1 and miRNAs that regulate doxorubicin (Dox) resistance in BC remain elusive. MATERIALS AND METHODS: Expression of TUG1 and miR-9 was measured by real-time PCR. EIF5A2 (eukaryotic translation initiation factor 5A-2) was detected by Western blot. Transfection of siRNAs or miRNA inhibitors was applied to silence lncRNA TUG1, eIF5A2 or miR-9. Cell viability, proliferation, and apoptosis were determined by CCK-8 (cell counting kit-8), flow cytometry, and EdU (5-ethynyl-2'-deoxyuridine) assays, respectively. The regulatory relationship between TUG1 and miR-9 was determined by a luciferase assay. RESULTS: LncRNA TUG1 was highly expressed in BC tissues and positively associated with Dox resistance in BC cell lines. SiRNA knockdown of TUG1 reversed Dox resistance in MCF-7/ADR cells. Mechanistically, TUG1 acted as a "sponge" for miR-9 and downregulated miR-9. Treatment with a miR-9 inhibitor blocked the effect of TUG1 siRNA, and knockdown of TUG1 inhibited the effects of miR-9. Furthermore, TUG1 inhibition of apoptosis induced by Dox involved miR-9 targeting of eIF5A2. CONCLUSION: TUG1 modulates the susceptibility of BC cells to Dox by regulating the expression of eIF5A2 via interacting with miR-9. These results indicate that the lncRNA TUG1 may be a novel therapeutic target in breast cancer.

[Establishment and characteristics of acute lung injury model induced by cigarette smoke in ICR mice].

OBJECTIVE: To develop a mouse model of acute lung injury induced by cigarette smoke (CS) and to investigate inflammatory changes with the model. METHODS: ICR mice exposed to CS for 20-min, 3/d. Bronchoalveolar lavage fluid (BALF) and lung tissue were harvested at d 0, d 1, d 3 and d 7 after CS exposure. Neutrophil count in BAFL, TNF-alpha and MMP-12 levels, the activity of MPO in lung tissue were determined. RESULT: Neutrophil count in BALF, MMP-12 and MPO levels in lung tissue were increased after CS exposure in a time-dependent manner with a peak at d3. TNF-alpha level sharply increased at d1, and remained high level until d7. CONCLUSION: ICR mice are tolerant and sensitive to CS exposure, which may be used as an appropriate animal model for acute lung injury induced by cigarette smoke.

MiR-340 suppresses cell migration and invasion by targeting MYO10 in breast cancer.

Breast cancer is one of the most common malignant tumors among females, and can seriously affect the physical and mental health and even threaten the lives of women. Recently, research has demonstrated that microRNAs (miRNAs), as a new method of regulation, have been shown to have oncogenic and tumor­suppressive functions in human breast cancer. Detection of their expression may lead to the identification of novel markers for breast cancer. In the present study, we firstly detected miR­340 expression and found lower expression of miR­340 in 6 human breast cancer cell lines by using RT­qPCR. Then by using wound healing assay and Transwell migration and invasion experiments, we focused on the role of miR-340 in the regulation of tumor cell migration and invasion, exploring the relationship between them. The results revealed that induction of miR­340 expression was able to suppress tumor cell migration and invasion, whereas knockdown of miR­340 expression promoted breast cancer cell migration and invasion. At the gene level, MYO10 (myosin X), as a direct miR­340 target gene, mediated the cell migration and invasion. Finally, we verified our research further at the tissue specimen level and in animal experiments. In brief, miR­340 plays an important role in breast cancer progression. Thus, miR­340 may be further explored as a novel biomarker for breast cancer metastasis and prognosis, and potentially a therapeutic target.

Neurofibroma and Pectoralis Muscle Hypoplasia: A Mild Degree of Poland's Syndrome.

BACKGROUND: Poland's Syndrome (PS) is a rare congenital syndrome characterized by the unilateral partial or complete absence of the sternocostal head of the pectoralis major muscle and ipsilateral brachysyndactyly or syndactyly of the fingers. It has been reported to be associated with other diseases, but PS accompanied by neurofibroma has rarely been reported. CASE REPORT: We report a rare case of a 16-year-old man with neurofibroma of the left breast accompanied by PS. Physical examination showed a mass in the left breast with skin hyperpigmentation and increased body hair. Intraoperative exploration showed a mass measuring 3-4 cm between the dysplastic pectoralis major and minor muscles. Pathologic examination of the resected mass showed cutaneous diffuse neurofibroma. A simple left mastectomy was performed. The postoperative course was uneventful with no evidence of recurrence at 4 months. CONCLUSION: Neurofibroma may also be accompanied by PS and should be differentiated from gynecomastia when a tumor grows in the breast.

Pro-apoptotic and anti-proliferative effects of mitofusin-2 via Bax signaling in hepatocellular carcinoma cells.

Mitochondrial GTPase mitofusin-2 (Mfn2) is a novel gene that remarkably suppresses the injury-mediated proliferation of vascular smooth muscle cells (VSMCs) and has a potential apoptotic effect via the mitochondrial apoptotic pathway. Hepatocellular carcinoma (HCC) tissues and matched normal tissues were examined for mfn2 expression. HCC cells were infected with adenovirus carrying Mfn2 (Ad-mfn2) or green fluorescent protein (Ad-GFP), used as a control. Short hairpin RNA (shRNA) was formed by shR-mfn2 and shR-Bax to repress mfn2 and Bax transcription, respectively. The effects of mfn2 on cell cycle distribution and apoptosis were measured by flow cytometric analysis. Significant downregulation of mfn2 was observed in HCC tissues compared with nearby normal tissues. Overexpression of mfn2 inhibited HCC cell proliferation and induced apoptosis by increasing the level of active caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage. Overexpression of mfn2 also induced cytochrome c release to the cytoplasm by enhancing Bax translocation from the cytoplasm to the mitochondrial membrane. Upregulation of mfn2 promoted apoptosis of HCC cells, and this was dramatically suppressed by shR-Bax. Our results show that the mfn2 gene is a potential tumor suppressor target that may significantly promote apoptosis via Bax and may inhibit proliferation in HCC cells. This gene may be an important therapeutic target for the treatment of tumors or hyperproliferative diseases.

Action of a Novel PDE4 inhibitor ZL-n-91 on lipopolysaccharide-induced acute lung injury.

In the present study, we investigated the effect of classic PDE4 inhibitor rolipram and novel PDE4 inhibitor ZL-n-91 on LPS-induced acute lung injury (ALI) in mice and its mechanism. ALI was induced in ICR mice by instilling intratracheally with LPS, and mice were divided into seven groups: control (Saline), LPS group, ZL-n-91 (3 microg, 10 microg, and 30 microg kg(-1), ip), Rolipram (1.0 mg kg(-1), ip) and dexamethasone (0.5 mg kg(-1), ip). After the 6h of instilling intratracheally with LPS in mice, total leukocyte number, neutrophil number and protein content in BALF increased rapidly, a large number of neutrophil infiltration around the pulmonary vessel and airway, the lung wet weight/dry weight (w/d)ratio raised significantly. MPO activity, TNF-alpha level and cAMP-PDE, PDE4 activity in lung homogenate raised significantly. P(a)O(2), P(a)CO(2) and PH value in peripheral arterial blood also changed obviously, P(a)O(2) and PH value dropped slightly and P(a)CO(2) increased significantly in LPS group. ZL-n-91 (3 microg, 10 microg, 30 microg kg(-1)) dose-dependently reduced the total leukocyte number, neutrophil number and total protein content in BALF, MPO activity, TNF-alpha level and cAMP-PDE, PDE4 activity in lung homogenate, but the effect of ZL-n-91 in pathological changes and lung wet w/d ratio is slight; Rol and Dex significantly reduced lung wet w/d ratio and improved pathological changes, neutrophil around the pulmonary vessel and airway significantly reduced, symptoms of lung edema relieved; The PH value, P(a)O(2) and P(a)CO(2) in ZL-n-91 high dosage group and Rol group had changes, but there was no significant difference compared with LPS group or saline group; After the administration, the righting reflex recovery time significantly shorten in every group of ZL-n-91. the righting reflex recovery time of Rol group was similar with ZL-n-91 30 microg kg(-1) group, while Dex group was similar with saline group. The present study confirms that the inhibitory effect of ZL-n-91(30 microg kg(-1)) on the inflammatory reactivity, including inhibition of inflammatory cell and protein exudation, MPO and PDE4 activity, improvement of the blood gas, those effects were equivalent with rolipram 1 mg kg(-1), and suggested that ZL-n-91 was stronger than rolipram in PDE4 inhibition. So we speculated that ZL-n-91 may have stronger therapeutic potential for treatment of inflammatory disease than rolipram, meantime have stronger nervous system effect than rolipram.