Background Epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis with the involvement of microRNAs (miRNAs). This study aims to assess the role of miR-506 working in tandem with LIM Homeobox 2 (LHX2) in EMT and metastasis through the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma (NPC). Methods Differentially expressed genes associated with NPC were screened using microarray analyses, from which LHX2 was identified. Next, the potential relationship between miR-506 and LHX2 was analyzed. In order to explore the effect of miR-506 or LHX2 on NPC cell proliferation, migration, invasion and apoptosis, serials of mimics, inhibitors or siRNA against LHX2 were transfected into NPC cells. Then, the expression patterns of LHX2, Wnt1, β-catenin, E-cadherin, Vimentin, TCF4 and Twist were determined to assess the influence of miR-506 or LHX2 on EMT as well as the relationship between the Wnt/β-catenin signaling pathway and TCF4. The tumorigenicity and lymph node metastasis (LNM) in xenograft tumors of nude mice were observed. Results The has-miR-506-3p was identified as the down-regulated gene in NPC based on the microarray data while LHX2 was negatively regulated by miR-506. Over-expression of miR-506 or silencing of LHK2 inhibited NPC cell proliferation, migration, invasion, tumorigenicity and LNM but promoted apoptosis indicated by decreased Wnt1, β-catenin, Vimentin, TCF4 and Twist expressions along with increased E-cadherin expressions. Conclusions miR-506 inhibits tumor growth and metastasis in NPC via inhibition of Wnt/β-catenin signaling by down-regulating LHX2, accompanied by decreased TCF4. Taken together, miR-506 targeted-inhibition LHX2 presents a promising therapeutic strategy for the treatment of NPC. Trial registration ChiCTR1800018889 . Registered 15 October 2018. Electronic supplementary material The online version of this article (10.1186/s13046-019-1023-4) contains supplementary material, which is available to authorized users.
Nasopharyngeal carcinoma (NPC) is a malignant epithelial cancer of the head and neck with high prevalence in southern China, which is accompanied by notable invasiveness and metastasis. Long noncoding RNAs (lncRNAs) participate in the progression of various cancers including NPC. Microarray‐based analysis identified highly expressed lncRNA mothers against decapentaplegic homolog 5 (SMAD5)‐antisense RNA 1 (AS1) related to NPC. Interestingly, it is found that SMAD5‐AS1 competitively bound to microRNA (miR)‐106a‐5p to regulate SMAD5. Herein, the study aimed to clarify the role of SMAD5‐AS1/miR‐106a‐5p/SMAD5 axis in the process of epithelial mesenchymal transition (EMT) in NPC. SMAD5‐AS1 was highly expressed and miR‐106a‐5p was poorly expressed in NPC tissues and cell lines. The NPC cells were treated with a series of small interfering RNAs, mimics, or inhibitors to explore the effects of SMAD5‐AS1, SMAD5, and miR‐106a‐5p on EMT, cell proliferation, migration, and invasion in NPC. Of note, SMAD5‐AS1 silencing or miR‐106a‐5p overexpression reduced expression of N‐cadherin, matrix metallopeptidase 9, Snail, and Vimentin while elevating E‐cadherin expression, thus inhibiting EMT, cell proliferation, migration, and invasion in NPC by down‐regulation of SMAD5. Moreover, SMAD5 silencing could reduce the ability of EMT induced by SMAD5‐AS1 up‐regulation. SMAD5‐AS1 silencing or miR‐106a‐5p elevation inhibited tumorigenesis in nude mice. Taken together, SMAD5‐AS1 silencing suppressed EMT, cell proliferation, migration, and invasion in NPC by elevating miR‐106a‐5p to down‐regulate SMAD5, which provided a novel therapeutic target for NPC treatment.—Zheng, Y.‐J., Zhao, J.‐Y., Liang, T.‐S., Wang, P., Wang, J., Yang, D.‐K., Liu, Z.‐S. Long noncoding RNA SMAD5‐AS1 acts as a microRNA‐106a‐5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma. FASEB J. 33, 12915–12928 (2019). http://www.fasebj.org
Currently, it is founded that under unidirectional wind and certain landform, composite insulators are always fanshaped non-uniformly polluted. In this paper, artificial pollution tests on three types of composite insulators with different shed configurations and under various fan-shaped non-uniform pollution conditions were carried out. Then the flashover performances of composite insulators, porcelain insulators and glass insulators were compared. Results indicate that there is a big difference between ac flashover performance of composite insulators under non-uninform pollution and uninform pollution. The flashover voltage of composite insulator is largely influenced by salt deposit density (SDD), the ratio of SDD of windward side to leeward side (W/L), the occupation ratio of leeward side k and the shed configurations. The relationship between SDD and U 50 still meets negative power function when composite insulator is fan-shaped non-uninform polluted. There is a reduction of 17.8-27.6% in the flashover strength when the ratio W/L of SDD decreases from 1/1 to 1/15. The shed configurations of composite insulators have great effects on the flashover performance. Composite insulators always have better withstand property compared to glass and porcelain insulators under either uniform pollution or fan-shaped non-uniform pollution.
A running traffic train induces piston wind in the subway. The influence of piston wind on fire smoke propagation in subway is investigated numerically. The flow field structure in fire platform, temperature contours and velocity profiles at certain positions are obtained at various scenarios respectively. Three methods are adopted to reduce the impact of piston wind on smoke layers. Results show that large-scale vortexes and tremendous horizontal inertial force would be produced under the influence of piston wind; and that smoke stratification would be broken totally under its influence, therefore toxic gas would spread to subway hall through stairs. So the former smoke management system in a subway station becomes less effective. Results also show that combination of enhanced the volume flux of pressurization at the subway hall and lowering the height of smoke screens around stairs are necessary to restrict hazard smoke on the floor on fire. The bypass wind tunnel and ventilation shaft are useful to attenuate the magnitude of piston wind.
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