[Retracted] Downregulation of long non­coding RNA GAS5 promotes cell proliferation, migration and invasion in esophageal squamous cell carcinoma.

[This retracts the article DOI: 10.3892/ol.2018.8797.].

MiR-106b-5p regulates esophageal squamous cell carcinoma progression by binding to HPGD.

BACKGROUND: Several studies have documented the key role of microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Although the expression of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene and miR-106b-5p are reportedly linked to cancer progression, their underlying mechanisms in ESCC remain unclear. METHODS: mRNA and miRNA expression in ESCC tissues and cells were analyzed using RT-qPCR. Luciferase and RNA pull-down assays were used to identify the interaction between miR-106b-5p and HPGD. Xenograft and pulmonary metastasis models were used to assess tumor growth and metastasis. CCK-8, BrdU, colony formation, adhesion, cell wound healing, Transwell, and caspase-3/7 activity assays, and flow cytometry and western blot analyses were used to examine the function of miR-106-5p and HPGD in ESCC cell lines. RESULTS: The findings revealed that miR-106b-5p expression was upregulated in ESCC tissues and cell lines. miR-106b-5p augmented cellular proliferation, colony formation, adhesion, migration, invasion, and proportion of cells in the S-phase, but reduced apoptosis and the proportion of cells in G1-phase. Silencing of miR-106-5p inhibited tumor growth in vivo and pulmonary metastasis. Although HPGD overexpression suppressed proliferation, colony formation, adhesion, migration, and invasion of ESCC cells, it promoted apoptosis and caused cell cycle arrest of the ESCC cells. The results also indicated a direct interaction of HPGD with miR-106b-5p in ESCC cells. Furthermore, miR-106b-5p inhibited HPGD expression, thereby suppressing ESCC tumorigenesis. CONCLUSION: Our data suggest that miR-106b-5p enhances proliferation, colony formation, adhesion, migration, and invasion, and induces the cycle progression, but represses apoptosis of ESCC cells by targeting HPGD. This suggests that the miR-106b-5p/HPGD axis may serve as a promising target for the diagnosis and treatment of ESCC.

miR-19a-3p Facilitates Lung Adenocarcinoma Cell Phenotypes by Inhibiting TEK.

Background: TEK and miR-19a-3p have been reported to regulate lung adenocarcinoma (LUAD) progression. However, the association between TEK and miR-19a-3p in LUAD remained unknown. This research investigated a novel miR-19a-3p/TEK interactome in LUAD cells. Materials and Methods: The mRNA expression and protein expression in the cell lines were determined using qPCR and Western blot assay, respectively. CCK-8 assay, EDU assay, flow cytometry cell apoptosis assay, scratch assay, and cell-to-extracellular matrix adhesion assay were performed to detect the proliferation, apoptosis, migration, and adhesion ability of A549 and H1975 cell lines. Results: Findings revealed that both mRNA and protein levels of TEK were downregulated in the LUAD tumor tissues and cell lines. It was also found that compared with the control group, the transfection of TEK overexpression plasmids into H1975 and A549 cell lines significantly inhibited cancerous phenotypes. However, experimental results indicated that by downregulating TEK, miR-19a-3p promoted LUAD cell phenotypes. Conclusion: This research demonstrated that an interactome existed between miR-19a-3p and TEK and that miR-19a-3p could suppress LUAD tumors by inhibiting TEK. This novel interactome could be used as a novel therapy target for LUAD.

Development of self-tuned diamond milling system for fabricating infrared micro-optics arrays with enhanced surface uniformity and machining efficiency.

Infrared micro-optics arrays (MOAs) featuring large numbers of micro-freeform lenslet are required increasingly in advanced infrared optical systems. Ultra-precision diamond cutting technologies have been widely used to fabricate MOAs with high form accuracy. However, the existing technologies can easily cause the non-uniformly fractured surface of infrared MOAs, due to the inherent low fracture toughness and high anisotropy of infrared materials as well as the time-varying chip thickness induced by ever-changing height and slope of the desired MOAs. In this study, a novel self-tuned diamond milling (STDM) system is proposed to achieve the ductile cutting of infrared MOAs with enhanced the surface uniformity and machining efficiency, and the corresponding toolpath planning algorithm is developed. In STDM system, a dual-axial fast servo motion platform is integrated into a raster milling system to self-adaptively match the maximum chip thickness for each tool rotational cycle with the critical depth of cut of the infrared material according to the local surface topography, thereby obtaining crack-free lenslet with high surface uniformity. Practically, micro-aspheric MOAs free from fractures are successfully machined on single-crystal silicon, a typical infrared material, to validate the proposed cutting concept. Compared with the conventional diamond milling, the proposed STDM is demonstrated to be able to avoid the non-uniform fractures without needing to reduce feed rate, and a smaller surface roughness of 4 nm and nearly double machining efficiency are achieved.

Flexible fabrication of micro-optics arrays with high-aspect-ratio by an offset-tool-servo diamond machining system.

Micro-optics arrays (MOAs) with high aspect ratio (AR) have unique advantages in realizing the minimization of optical systems by reducing the focal distance. Fast or slow tool servo (F/STS) is widely regarded as an outperforming technique for the fabrication of MOAs featuring high form accuracy. However, in the machining of MOAs with high AR, the non-smooth cutting trajectory of F/STS inevitably leads to intensive tool vibrations and the interference between the tool flank face and the finished surface, thereby deteriorating surface roughness. In this study, a novel offset-tool-servo (OTS) diamond machining technology and the corresponding toolpath generation algorithm are proposed to achieve the flexible fabrication of micro-freeform lens arrays with high AR. In OTS, with the assistance of four-axis servo motions, a spiral toolpath is generated for each single lenslet, which effectively avoids the tool interference induced by the steep descending movement of the tool in F/STS. Besides, the proposed machining strategy well ensures the smoothness of the generated toolpath for each lenslet, thereby effectively avoiding the destruction of the surface quality induced by the tool vibrations. In practice, this method is validated by fabricating different MOAs with aspheric and freeform structures. Compared with F/STS, the OTS method is demonstrated to be able to achieve two times larger AR values, and smoother and more uniform surface quality are simultaneously achieved.

One-step generation of hybrid micro-optics with high-frequency diffractive structures on infrared materials by ultra-precision side milling.

Hybrid micro-optics of infrared (IR) materials are of great advantage in realizing the function integration and minimization of advanced IR optical systems. However, due to the hard-and-brittle nature of IR materials, it is still challenging for both non-mechanical and mechanical technologies to achieve one-step generation of hybrid infrared micro-optics with high form accuracy. In the present study, a flexible method, namely ultra-precision side milling (UPSM), is first introduced to achieve one-step generation of infrared hybrid micro-optics in ductile mode, and the corresponding reflective diffraction characteristics are analyzed. In UPSM, the reflective/refractive primary surface of the hybrid micro-optics is formed via the removal of workpiece material, and the high-frequent secondary diffractive micro/nanostructures are simultaneously generated by the tool residual marks of cutting trajectories. With the consideration of the changing curvature of the primary surface, the optimal toolpath generation strategy is introduced to acquire the desired shapes of the secondary micro/nanostructures, and the selecting criteria of the machining parameters is discussed to avoid the brittle fractures of IR materials. In practice, two types of hybrid micro-optic components, namely hybrid micro-aspheric arrays and sinusoid grid surface with high-frequent secondary unidirectional phase gratings, are successfully fabricated on single-crystal silicon to validate the proposed method. The method adopted in this study is very promising for the deterministic fabrication of hybrid micro-optics on infrared materials.

Effect of Machining Parameters and Tool Wear on Surface Uniformity in Micro-Milling.

In micro-milling, the periodically varying chip thickness, which varies with tool rotation, leads to varying degrees of minimum chip thickness effect and ploughing effect during surface generation. This results in a change of roughness in the cross-sectional direction of the micro-grooves, giving a non-uniform surface quality. However, the factors influencing surface uniformity in micro-milling are not fully understood. In the present work, the effect of the machining parameters and tool wear on surface uniformity in micro-milling is theoretically and experimentally studied. A mathematical model is proposed to predict the varying surface roughness in the cross-sectional direction of the micro-grooves, which is experimentally validated by fabricating a set of 800 µm wide micro-grooves. The theoretical and experimental results reveal that, compared to the normally adopted Ra or Sa, the relative standard deviation of roughness (RSDS) is more appropriate to evaluating surface uniformity. When machining under small feed rates and small cutting depths, the surface uniformity deteriorates as the feed rate increases and improves as the cutting depth increases. The blunt cutting edge induced by tool wear enhances the surface uniformity and increases the surface roughness at the same time. This research furthers understanding of the various cutting mechanisms in micro-milling and can be applied to the optimization of machining parameters in micro-milling.

Downregulation of long non-coding RNA GAS5 promotes cell proliferation, migration and invasion in esophageal squamous cell carcinoma.

The present study aimed to investigate the potential role of long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) in the progression of esophageal squamous cell carcinoma (ESCC) and to reveal its possible regulatory mechanism. The expression of lncRNA GAS5 in ESCC tissues and cell lines was analyzed using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The overexpression vector pc-GAS5 and control vector pc-negative control (NC), containing no GAS5 sequence, were transfected into ESCC cells. The effects of lncRNA GAS5 overexpression on cell proliferation, cell cycle distribution, cell migration and invasion were then analyzed. Besides, the expression levels of ATM-CHK2 pathway-associated proteins and epithelial-mesenchymal transition (EMT)-associated proteins were measured. Expression of lncRNA GAS5 was downregulated in the ESCC tissues compared with adjacent normal tissues, and was also downregulated in ESCC Kyse450 cells compared with the human esophageal epithelial HET-1A cell line. Additionally, lncRNA GAS5 was successfully overexpressed in ESCC cells following transfection with pc-GAS5. Overexpression of lncRNA GAS5 significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and suppressed cellular migration and invasion. When cells were transfected with pc-GAS5, the levels of phosphorylated (p)-ATM serine/threonine protein kinase, p-checkpoint kinase 2 (CHK2), p-cell division cycle 25C, p-cyclin-dependent kinase 1, N-cadherin, vimentin and Snail were significantly increased, whereas that of E-cadherin were markedly decreased. The results of the present study indicate that overexpression of lncRNA GAS5 may inhibit cell proliferation, migration and invasion in ESCC. lncRNA GAS5 overexpression may induce cell cycle arrest at G2/M stage by activating the ATM-CHK2 pathway. The results of the current study further indicate that lncRNA GAS5 overexpression may suppress cell migration and invasion via EMT-associated proteins. lncRNA GAS5 could therefore serve as a potential target for ESCC therapy.

Sanguinarine exhibits antitumor activity via up-regulation of Fas-associated factor 1 in non-small cell lung cancer.

Lung cancer is the most common type of malignancy and one of the leading causes of cancer-related deaths in the world. Non-small cell lung carcinomas (NSCLC) account for 85% cases of lung cancer. Sanguinarine (SNG) is a benzophenanthridine alkaloid isolated from plants of the Papaveraceae family that possess diverse biological activities. SNG exhibits antitumor effects in several cancer cells. However, the effects of SAN on NSCLC proliferation, invasion, and migration and the mechanisms remain to be clarified. We showed that SNG concentration- and time-dependently decreased the cell proliferation, viability, and induced a marked increase in cell death in A549 cells. SNG inhibited invasion and migration and induced S phase cell cycle arrest and apoptosis. SNG resulted in a significant increase of E-cadherin expression and a marked decrease of the expression of N-cadherin, Vimentin, Smad2/3, and Snail and the phosphorylation of Smad2. SNG increased Fas-associated factor 1 (FAF1) expression and upregulation of FAF1 inhibited cell proliferation, invasion, and migration and induced cell cycle arrest and apoptosis in NSCLC cells. Knockdown of FAF1 suppressed SNG-induced inhibition of cell proliferation, invasion, and migration and induction of cell cycle arrest and apoptosis in NSCLC cells. SNG also inhibited implanted tumor growth and increased FAF1 expression in tumors in vivo. Our findings highlight FAF1 as a novel therapeutic target and provide a new insight in the potential use of SNG for the inhibition of NSCLC.