A giant breast malignant solitary fibrous tumor: A rare case report and brief review.

Solitary fibrous tumors (SFTs), which were first identified in the pleura and later at multiple anatomical locations, are rare mesenchymal neoplasms. The characteristics of SFTs include well-circumscribed margins, intense vascularity and a relatively indolent clinical course. SFTs originating from the breast are rare. To the best of our knowledge, only 33 cases of breast SFTs, including five malignant tumors, have been reported to date. In the present study, a rare case of complete resection of a giant malignant SFT is reported. A 48-year-old female patient who visited Weifang People's Hospital (Weifang, China) had a 2-year history of a right palpable breast lesion. The patient reported no other symptoms, such as skin changes or nipple discharge. An ultrasound examination revealed a giant, well-circumscribed, heterogeneous and hypoechoic lesion with central and peripheral blood flow. Owing to the large size of the lesion, mammography and magnetic resonance imaging were not feasible. Core needle biology showed that the lesion was a malignant spindle cell tumor. Following this, mastectomy and sentinel lymph node biopsy were performed. The sentinel lymph nodes exhibited metastasis. A definitive diagnosis of malignant SFT was made by microscopic examination with immunohistochemistry. The treatment strategy for benign breast SFTs should be complete surgical excision, whereas for malignant SFTs, it should include radical resection along with radiotherapy and chemotherapy. Owing to the indolent nature and late recurrence and metastasis of malignant breast SFTs, regular patient follow-up for a longer duration is essential.

LINC00313/miR-4429 axis provides novel biomarkers for the diagnosis and prognosis of non-small cell lung cancer.

BACKGROUND: Increasing evidence suggests that the LncRNA/miRNA axis plays a key role in many types of tumorigenesis. However, the potential role and clinical value of LINC00313/miR-4429 in non-small cell lung cancer (NSCLC) remain elusive and need further study. The aim of this study was to investigate the role of LINC00313/miR-4429 axis in NSCLC. METHODS: The expression of LINC00313 and miR-4429 in serum, tissues and cell lines of NSCLC patients were detected by reverse transcription-quantitative PCR. The diagnostic value was evaluated by receiver operating characteristic (ROC) curve analysis and the prognostic value was analyzed by Kaplan-Meier survival analysis and Cox regression. RESULT: The expression of LINC00313 was significantly up-regulated while the expression of miR-4429 was down-regulated in NSCLC serum, tissue and cell lines. A negative correlation was found between LINC00313 and miR-4429 in patients with NSCLC. ROC curves showed that LINC00313 and miR-4429 had high diagnostic value and Kaplan-Meier curve results showed that high expression of LINC00313 and low expression of miR-4429 predicted poor prognosis. CONCLUSION: In summary, our data show that the ectopic expression of LINC00313 and miR-4429 has promising clinical significance in the diagnosis and prognosis of NSCLC. The LINC00313/miR-4429 axis may provide novel biomarker for NSCLC treatment.

Temperature compensation design and experiment for a giant magnetostrictive actuator.

Because the performance of giant magnetostrictive materials (GMMs) can vary at different temperatures, the positioning accuracy of a giant magnetostrictive actuator is affected by heat. In this work, a new simplified control strategy under compulsory water cooling is proposed to maintain a constant GMM temperature. Based on this strategy, a coupled turbulent flow field and temperature field finite element model is created for a GMM smart component. The model is simulated using COMSOL Multiphysics software version 5.3. Through simulations, the temperature field distribution of GMM smart components is analysed under different drive input currents and cooling water flow rates. Based on the obtained simulation results, a GMM intelligent component temperature control device is constructed. The experimental results are in good agreement with the simulation results; a thermostatic control effect is achieved in the thermostat of the giant magnetostrictive rod. Thus, the proposed temperature control strategy is proven effective via simulations and experiments.

Circular RNA circABCC4 regulates lung adenocarcinoma progression via miR-3186-3p/TNRC6B axis.

Lung adenocarcinoma (LUAD), a general kind of bronchogenic malignancy globally, is depicted as one of the most critical factors affecting human health severely. Featured with loop structure, circular RNA (circRNA) has been described as an essential regulator of multiple human malignancies. Nevertheless, knowledge concerning the regulatory function of circRNA in LUAD progression remains limited. Identified as a novel circRNA, circABCC4 has not been studied in LUAD as yet. This is the first time to probe into the underlying role of circABCC4 in LUAD. In this study, a notably elevated expression of circABCC4 was found in LUAD tissues and cells. Besides, circABCC4 is verified to be characterized with a circular structure in LUAD. Functional assays elucidated that knockdown of circABCC4 significantly impaired LUAD cell proliferation, migration as well as accelerated cell apoptosis. Molecular mechanism experiments later revealed that circABCC4 could bind with miR-3186-3p and miR-3186-3p was a tumor suppressor in LUAD. Moreover, TNRC6B was validated to combine with miR-3186-3p, and its expression was respectively negatively and positively regulated by miR-3186-3p and circABCC4 in LUAD. Final rescue experiments further delineated that TNRC6B upregulation partially restored circABCC4 downregulation-mediated effect on LUAD progression. In sum, circABCC4 regulates LUAD progression via miR-3186-3p/TNRC6B axis.

MicroRNA-761 inhibits the metastasis of gastric cancer by negatively regulating Ras and Rab interactor 1.

Gastric cancer (GC), the second most common malignant cancer worldwide, gives rise to a number of cancer-associated fatalities annually. Accumulating evidence has shown that microRNAs (miRs) may serve as oncogenes or tumor suppressors in GC development. The aim of this study was to discover the expression, function and mechanism of miR-761 in GC progression. First, the findings revealed that the expression level of miR-761 was significantly decreased in GC cell lines and tissues. The functional studies showed that miR-761 in GC cells inhibited tumor proliferation and metastasis. In the mechanistic study, through an online database search and luciferase assay, Ras and Rab interactor 1 (RIN1), which has been demonstrated as an oncogene in various types of cancer, including GC, was identified as a target of miR-761. Notably, miR-761 expression was demonstrated to be negatively correlated with RIN1 mRNA levels in GC tissues. Simultaneously, overexpression of RIN1 partially rescued the inhibitory effect of miR-761 mimic in the GC cells. The present study provided new insights into the role of miR-761 in the progression of GC, and implicated the potential application of miR-761 in GC cell therapy.

LARP7 in papillary thyroid carcinoma induces NIS expression through suppression of the SHH signaling pathway.

The incidence of thyroid cancer has increased the past few decades, the most frequent type has been identified to be the papillary thyroid carcinoma (PTC). Following thyroidectomy, radioiodine ablation treatment on PTC is routinely performed. However, many patients do not benefit from radioiodine therapy. Therefore, novel targeted therapies to suppress tumor growth and improve radioiodine uptake are required. La ribonucleoprotein domain family member (LARP)7 is a member of the LARP family and functions as a potential suppressor of the progression of carcinoma. In the present study, the expression status of LARP7 in PTC tissues and cell lines was investigated, and the cell viability, proliferation and apoptotic rate, radioiodine uptake ability of PTC cells with overexpression of LARP7 in vitro was determined. Expression levels of LARP7 were significantly downregulated in PTC tissues and cell lines. Overexpression of LARP7 inhibited the proliferation and increased the radioiodine uptake ability of PTC cells in vitro and inhibited the tumor growth in vivo. Furthermore, LARP7 overexpression inhibited the sonic hedgehog (SHH) signaling pathway and increased sodium/iodide symporter (NIS) expression. However, treatment with recombinant human SHH partially reduced radioiodine uptake ability and NIS expression induced by LARP7. In conclusion, LARP7 may act as a tumor suppressor in PTC by inhibiting the SHH signaling pathway and may be a promising therapeutic target in patients with PTC.

Hsa-miR-599 suppresses the migration and invasion by targeting BRD4 in breast cancer.

Breast cancer is the second leading cause of cancer-associated mortality in females in the USA. Hsa-miR-599 was demonstrated to function as a tumour suppressor during cancer progression. However, the function and mechanism of the hsa-miR-599 in human breast cancer remain elusive. Thus, the aim of the present study was to investigate the potential role of hsa-miR-599 in breast cancer biology. The expression levels of hsa-miR-599 in 40 pairs of surgical specimens and human breast cancer cell lines were detected using quantitative polymerase chain reaction analysis. The overexpression of hsa-miR-599 was established by transfecting mimics into the MCF-7 and MDA-MB-231 cell lines. Cell counting kit-8, colony formation and transwell assays were used to investigate the potential function of hsa-miR-599 in MCF-7 and MDA-MB-231 cell lines. Luciferase assays combined with western blot analysis was performed to validate the regulation of a putative target of hsa-miR-599. The results demonstrated that hsa-miR-599 was downregulated in the breast cancer tissues and breast cancer cell lines. Overexpression of hsa-miR-599 was revealed to inhibit the viability and proliferation of cell in vitro and tumour growth in vivo. The results of the luciferase assay indicate that bromodomain containing 4 (BRD4) is a direct target of hsa-miR-599. Furthermore, the xenograft mouse model demonstrated that overexpressed hsa-miR-599 reduced BRD4 expression. These results suggest that hsa-miR-599 serves as an oncosuppressive microRNA that impairs breast cancer tumorigenesis and progression by directly targeting BRD4. Furthermore, increased BRD4 expression partially reversed the suppressive effect of hsa-miR-599. In conclusion, the results of the present study demonstrated that hsa-miR-599 suppressed breast cancer progression by downregulating BRD4. The overexpression of hsa-miR-599 may be considered as a novel therapeutic target for the treatment of patients with breast cancer.

Antitumor action of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone in hepatocellular carcinoma.

The inhibition of apoptosis in cancer cells is the major pathological feature of hepatic carcinoma. Rosiglitazone (RGZ), a ligand for peroxisome proliferator-activated receptor γ (PPAR-γ), has been shown to induce apoptosis in hepatic carcinoma cells. However, the mechanism underlying this effect remains to be elucidated. The present study aimed to investigate the effect of RGZ on cell viability and apoptosis, and its mechanisms in cultured HepG2 cells using MTT assay, flow cytometry and western blotting. The results revealed that treatment with RGZ may attenuate HepG2 cell viability and induce the apoptosis of the cells. The mechanism of RGZ-induced apoptosis involves an increase in the level of activated PPAR-γ (p-PPAR-γ) and a decrease in p85 and Akt expression. In addition, the PPAR-γ antagonist GW9662 suppressed the effect of RGZ in the HepG2 cells. Taken together, the results suggest that RGZ induces the apoptosis of HepG2 cells through the activation of PPAR-γ, suppressing the activation of the PI3K/Akt signaling pathway. Such mechanisms may contribute to the favorable effects of treatment using RGZ in HepG2 cells.

BRD4 induces cell migration and invasion in HCC cells through MMP-2 and MMP-9 activation mediated by the Sonic hedgehog signaling pathway.

Hepatocellular carcinoma (HCC) is a highly aggressive form of carcinoma with poor prognosis, and HCC-associated mortality primarily occurs due to migration and invasion of HCC cells. The manipulation of epigenetic proteins, such as BRD4, has recently emerged as an alternative therapeutic strategy. The present study aimed to investigate the novel mechanism of BRD4 involvement in the migration and invasion of HCC cells. Reverse transcription-quantitative polymerase chain reaction was used to assess BRD4 mRNA expression levels in HCC cell lines. This analysis demonstrated that BRD4 was significantly overexpressed in HCC cell lines compared with a human immortalized normal liver cell line. A short hairpin RNA (shRNA) was then used to suppress BRD4 expression in HCC cells, and resulted in impaired HCC cell proliferation, migration and invasion. When the HepG2 HCC cell line was treated with recombinant human sonic hedgehog (SHH) peptide, the migration and invasion capabilities of HepG2 cells that were inhibited by BRD4 silencing were restored. BRD4 induced cell migration and invasion in HepG2 cells through the activation of matrix metalloproteinase (MMP)-2 and MMP-9, mediated by the SHH signaling pathway. Taken together, the results of the present study demonstrated the importance of BRD4 in HCC cell proliferation and metastasis. Thus, BRD4 is a potential novel target for the development of therapeutic approaches against HCC.

Effect of fractionated irradiation on the expression of multidrug resistance genes in the CNE1 human nasopharyngeal carcinoma cell line.

Nasopharyngeal carcinoma (NPC) often develops drug resistance following radiotherapy. The molecular basis of radiotherapy-related multidrug resistance (MDR) remains unclear. In the present study, we investigated the effect of fractionated irradiation on the expression of the MDR-1 gene and the MDR-associated protein P-glycoprotein (P-gp) in CNE1 human NPC cells. CNE1 cells were treated with fractionated X-rays. Drug resistance was determined by MTT assay. The expression levels of MDR-1 and P-gp were analyzed by RT-PCR and western blot analysis, respectively. Differential expression was analyzed by gene chips. The results revealed that low levels of mRNA expression of MDR1 were present in non-irradiated CNE1 cells. Compared with the control, the expression of MDR1 mRNA was gradually increased following fractionated irradiation. On day 21, the expression of MDR1 mRNA was increased 1.59- and 2.19-fold, compared with the control, by treatment with 10 and 20 Gy, respectively. We observed decreased MDR1 expression following treatment with 10 and 20 Gy irradiation on days 28 and 35, compared with day 21. On days 21, 28 and 35, expression was increased 1.37-, 1.40- and 1.15-fold by treatment with 20 Gy compared with 10 Gy. Expression of MDR1 was significantly upregulated by treatment with 50 Gy irradiation compared with the control on days 78 and 106. P-gp expression was consistent with that of MDR1 mRNA expression. The sensitivity of CNE1 cells to cisplatin was reduced following irradiation compared with the control. A total of 26 genes were significantly upregulated and 8 genes were significantly downregulated compared with the control. Results of the present study have shown that MDR1 and P-gp are upregulated in CNE1 cells following irradiation. Multiple genes were involved in the mechanism of radiation-induced drug resistance.

Hydrangeas-like Bi2WO6: facile synthesis, visible-light driven photocatalysis and theoretical analysis.

Hydrangeas-like Bi2WO6 powders were synthesized successfully by salt-ultrasonic assisted hydrothermal process, which were characterized by scanning electron microscopy (SEM), Energy dispersive X-ray (EDS), X-ray diffraction (XRD), and UV-visible diffuse reflectance spectra (UV-Vis DRS), respectively. Bi, W and O elements were contained in the product, which could be tested by EDS. The crystal structure of the catalyst was orthorhombic phase (JCPDS card no.73-1126). And the band gap was estimated to be 2.56 eV from the onset of UV-Vis absorption spectra of the catalyst. In addition, the photocatalytic activities of the products were investigated on the degradation of Rhodamine B (RhB). It demonstrated that photocatalysts exhibited excellent visible-light driven photocatalytic performance. And the target residue was less than 1% in 20 min under Xenon lamp irradiation. First-principles calculations based on density functional theory (DFT) were used to explore the electronic and optical properties of Bi2WO6. And the theoretical calculations could illustrate the photocatalytic performance of Bi2WO6 powders under visible light irradiation.

The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice.

BACKGROUND: Ets transcription factors have been widely implicated in the control of tumorigenesis, with most studies suggesting tumor-promoting roles. However, few studies have examined Ets tumorigenesis-modifying functions in vivo using model genetic systems. METHODS: Using mice expressing a previously characterized Ets dominant repressor transgene in the intestinal epithelium (Villin-En/Erm), we examined the consequences of blocking endogenous Ets-mediated transcriptional activation on tumorigenesis in the ApcMin model of intestinal carcinoma. RESULTS: En/Erm expression in the intestine, at levels not associated with overt crypt-villus dysmorphogenesis, results in a marked increase in tumor number in ApcMin animals. Moreover, when examined histologically, tumors from En/Erm-expressing animals show a trend toward greater stromal invasiveness. Detailed analysis of crypt-villus homeostasis in these En/Erm transgenic animals suggests increased epithelial turnover as one possible mechanism for the enhanced tumorigenesis. CONCLUSION: Our findings provide in vivo evidence for a tumor-restricting function of endogenous Ets factors in the intestinal epithelium.

Ets transcription factors control epithelial maturation and transit and crypt-villus morphogenesis in the mammalian intestine.

Members of the Ets transcription factor family are widely expressed in both the developing and mature mammalian intestine, but their biological functions remain primarily uncharacterized. We used a dominant repressor transgene approach to probe the function of epithelial Ets factors in the homeostasis of the crypt-villus unit, the functional unit of the small intestine. We show that targeted expression in small intestinal epithelium of a fusion protein composed of the Engrailed repressor domain and the Erm DNA-binding domain (En/Erm) results in marked disruption of normal crypt-villus homeostasis, including a cell-autonomous disturbance of epithelial maturation, increased epithelial transit, severe villus dysmorphogenesis, and crypt dysmorphogenesis. The epithelial maturation disturbance is independent of the regulation of TGFbetaRII levels, in contrast to Ets-mediated epithelial differentiation during development; rather, regulation of Cdx2 expression may play a role. The villus dysmorphogenesis is independent of alterations in the crypt-villus boundary and inappropriate beta-catenin activation, and thus appears to represent a new mechanism controlling villus architectural organization. An Analysis of animals mosaic for En/Erm expression suggests that crypt nonautonomous mechanisms underlie the crypt dysmorphogenesis phenotype. Our studies thus uncover novel Ets-regulated pathways of intestinal homeostasis in vivo. Interestingly, the overall En/Erm phenotype of disturbed crypt-villus homeostasis is consistent with recently identified Ets function(s) in the restriction of intestinal epithelial tumorigenesis.

Nuclear targeting of the CaMKII anchoring protein alphaKAP is regulated by alternative splicing and protein kinases.

alphaKAP is an anchoring protein for the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and is encoded within the same gene as the CaMKIIalpha isoform. alphaKAP co-assembles with CaMKII and targets such heteromers to the membrane of the sarcoplasmic reticulum, where CaMKII can regulate Ca(2+) homeostasis. CaMKII has also nuclear functions in skeletal muscle, however, the nuclear targeting mechanism has been elusive. We show here that developmentally regulated splicing of exon Ealpha(B) generates a functional nuclear localization signal (NLS) in alphaKAP(B), the dominant alphaKAP variant in mature muscle. The alphaKAP(A) variant lacks the NLS and dominates in developing muscle before and around birth. Both alphaKAP variants localize to membranes, but a small fraction of alphaKAP(B) is additionally found in the nucleus. Indeed, alpha-karyopherins that mediate nuclear import bound to alphaKAP(B) but not alphaKAP(A) in vitro. When the N-terminal membrane anchor of alphaKAP was deleted, localization of alphaKAP(B) but not alphaKAP(A) became predominantly nuclear. Co-expression of constitutively active CaMKI and IV, which do not bind to alphaKAP, interfered with nuclear localization of alphaKAP(B). CaMKIIalpha was found essentially exclusively in the cytoplasm when expressed in cell lines but was targeted to the nucleus when co-expressed with the nuclear form of alphaKAP(B). Thus, nuclear targeting of cytoplasmic CaMKII isoforms by alphaKAP may be regulated by developmentally controlled alternative splicing and by protein kinases.

Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer.

We show that atypical PKCiota, which plays a critical role in the establishment and maintenance of epithelial cell polarity, is genomically amplified and overexpressed in serous epithelial ovarian cancers. Furthermore, PKCiota protein is markedly increased or mislocalized in all serous ovarian cancers. An increased PKCiota DNA copy number is associated with decreased progression-free survival in serous epithelial ovarian cancers. In a Drosophila in vivo epithelial tissue model, overexpression of persistently active atypical PKC results in defects in apical-basal polarity, increased Cyclin E protein expression, and increased proliferation. Similar to the Drosophila model, increased PKCiota proteins levels are associated with increased Cyclin E protein expression and proliferation in ovarian cancers. In nonserous ovarian cancers, increased PKCiota protein levels, particularly in the presence of Cyclin E, are associated with markedly decreased overall survival. These results implicate PKCiota as a potential oncogene in ovarian cancer regulating epithelial cell polarity and proliferation and suggest that PKCiota is a novel target for therapy.