LINC02253 promote the malignant phenotype of Colon adenocarcinoma cells by up-regulating WWP1-mediated SMAD3 ubiquitination.

OBJECTIVES: Colon adenocarcinoma (COAD) represents a type of common malignant tumor originating in the digestive tract. Long non-coding RNAs (lncRNAs) have been identified to engage in regulating the initiation and development of COAD. LncRNA LINC02253 has been reported abnormal expressed in COAD, but the underlying mechanism has not been discussed so far. This study aimed to determine the role and the molecular biology mechanism of LINC02253 in COAD progression and unearthed its specific molecular mechanism. MATERIALS AND RESULTS: RT-qPCR and Western blot assays were conducted to detect gene expression. Function assays were performed to evaluate the effect of gene expression on COAD cell phenotype. Mechanism analyses were done to verify the association among genes after bioinformatics analysis. The obtained data revealed that LINC02253 demonstrated a high expression in COAD tissues and cells. This gene served as an oncogene, permitting to stimulate proliferation and suppress apoptosis of COAD cells. Mechanically, it was found that LINC02253 recruited FUS to stabilize WWP1 mRNA and WWP1 could mediate SMAD3 ubiquitination, thereby promoting the malignant phenotype formation of COAD cells. CONCLUSIONS: LINC02253 was uncovered to exert an oncogenic role, enhancing the proliferation of COAD cells and repressing the cell apoptosis by recruiting FUS and encouraging WWP1-mediated SMAD3 ubiquitination.

Pachymic acid alleviates experimental pancreatic fibrosis through repressing NLRP3 inflammasome activation.

Pachymic acid (PA), a natural triterpenoid, possesses the capacity to repress inflammatory and profibrotic responses. However, the role of PA in pancreatic fibrosis remains unclear. Here the effect of PA on anti-fibrogenic response was investigated using in vivo and in vitro pancreatitis models. We demonstrated that PA treatment repressed TGF-ß-induced pancreatic stellate cells (PSCs) activation in vitro, as evidenced by decreased expression of Collagen I, α-smooth muscle actin, and fibronectin. PA decreased Cerulein-induced acinar injury and pancreatic fibrosis in an experimental pancreatitis model. Mechanistically, PA repressed Cerulein or (TGF-ß)-induced activation of nuclear factor (NF)-κB signaling and thus decreased NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome activation in PSCs. Pharmacological inhibition of NLRP3 repressed TGF-ß-induced activation of PSCs. More important, NLRP3 activator partially attenuated the effect of PA on inhibiting PSCs activation. Collectively, these data demonstrate that PA represses PSCs activation and pancreatic fibrosis through repressing NF-κB/NLRP3 signaling.

Orchestrating a biomarker panel with lncRNAs and mRNAs for predicting survival in pancreatic ductal adenocarcinoma.

The low survival of patients with pancreatic ductal adenocarcinoma (PDAC) makes the treatment of this disease one of the most challenging task in modern medicine. Here, by mining a large-scale cancer genome atlas data set of pancreatic cancer tissues, we identified 21 long noncoding RNAs (lncRNAs) that significantly associated with overall survival in patients with PDAC (P < .01). Further analysis revealed that 8 lncRNAs turned out to be independently correlated with patients' overall survival, and the risk score could be calculated based on their expression. To obtain a better predicting power, we integrated lncRNA data with a total of 410 differently expressed messenger RNAs (mRNAs) screened from PDAC and normal tissues in gene expression omnibus (GEO) database. The integration resulted in a much better panel including 8 lncRNAs (RP3.470B24.5, CTA.941F9.9, RP11.557H15.3, LINC00960, AP000479.1, LINC00635, LINC00636, and AC073133.1) and 8 mRNAs (DHRS9, ONECUT1, OR8D4, MT1M, TCN1, MMP9, DPYSL3, and TTN) to predict prognosis. A functional evaluation showed that these lncRNAs might play roles in pancreatic secretion, cell adhesion, and proteolysis. Using normal and pancreatic cancer cell lines, we confirmed that a majority of identified lncRNAs and mRNAs showed altered expressions in pancreatic cancer cells. Especially, LINC01589, LINC00960, TCN1, and MT1M showed a profoundly increased expression in pancreatic cancer cells, which suggests their potentially important role in pancreatic cancer. The results of our work indicate that lncRNAs have vital roles in PADC and provide new insights to integrate multiple kinds of markers in clinical practices.

Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6.

AIM: To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. METHODS: Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. RESULTS: After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend (P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age (P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues (P < 0.05). CONCLUSION: Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation.

miR-340 Inhibits Proliferation and Induces Apoptosis in Gastric Cancer Cell Line SGC-7901, Possibly via the AKT Pathway.

BACKGROUND Gastric cancer is among the most common types of cancer, with high morbidity and mortality. MicroRNAs (miRNAs) play vital roles in the tumorigenesis and biology of gastric cancer. This study aimed to reveal the role of miR-340 in gastric cancer cell proliferation and apoptosis and to elucidate the potential mechanisms. MATERIAL AND METHODS Human gastric cancer cells SGC-7901 were used in this study for cell transfection with miR-340 mimic or inhibitor. After transfection, cell viability, proliferation, and apoptosis were examined by MTT, BrdU, and flow cytometry assays, respectively. The protein level changes of p27, p21, Caspase 3 (CASP3), B cell lymphoma 2 (BCL2), BCL2-associated X protein (BAX), and v-AKT murine thymoma viral oncogene (AKT) were detected by Western blot. RESULTS Overexpression of miR-340 significantly reduced cell viability and proliferation (P<0.01), and induced cell apoptosis (P<0.01) of SGC-7901. miR-340 elevated the protein level of cell cycle inhibitor p27, but did not affect the level of p21. Apoptosis-related factors pro-CASP3, cleaved-CASP3, and BAX were promoted, and BCL2 was inhibited by miR-340. miR-340 also suppressed the phosphorylation of AKT. Opposite effects were detected when SGC-7901 cells were transfected with miR-340 inhibitor. CONCLUSIONS These results indicate that miR-340 can inhibit proliferation and induce apoptosis of SGC-7901 cells, suggesting its roles in protecting against gastric cancer. The roles of miR-340 in gastric cancer cells may be associated with its regulation of the AKT pathway. Thus, miR-340 may be a potential therapeutic strategy for gastric cancer treatment.

Knockdown of Minichromosome Maintenance Proteins Inhibits Foci Forming of Mediator of DNA-Damage Checkpoint 1 in Response to DNA Damage in Human Esophageal Squamous Cell Carcinoma TE-1 Cells.

Esophageal squamous cell carcinoma (ESCC) has a high morbidity in China and its treatment depends greatly on adjuvant chemotherapy. However, DNA damage repair in cancer cells severely affects the outcome of treatment. This study investigated the potential mechanism regarding mediator of DNA-damage checkpoint 1 (MDC1) and minichromosome maintenance proteins (MCMs) during DNA damage in ESCC. Recombinant vectors of MDC1 and MCMs with tags were constructed and transfected into human ESCC cell line TE-1. Immunoprecipitation and mass spectrometry were performed to screen the MCMs interacting with MDC1, and direct interaction was confirmed by glutathione S-transferase (GST) pull-down assay in vitro. MCM2 and MCM6 were knocked down by shRNAs, after which chromatin fraction and foci forming of MDC1 upon bleomycin-induced DNA damage were examined. The results showed that MCM2/3/5/6 were immunoprecipitated by antibodies against the tag of MDC1 in TE-1 nuclei, and the GST pull-down assay indicated the direct interaction. Knockdown of MCM2 or MCM6 reduced the chromatin fraction of MDC1 according to Western blot results. Moreover, knockdown of MCM2 or MCM6 could significantly inhibit foci forming of MDC1 in TE-1 nuclei in response to bleomycin-induced DNA damage (p < 0.001). This study indicates the direct interaction between MDC1 and MCMs in TE-1 nuclei. Downregulation of MCMs can inhibit chromatin fraction and foci forming of MDC1 in TE-1 cells upon DNA damage, which suggests MCMs and MDC1 as potential targets to improve the outcome of chemotherapy in ESCC.

Tuning of resonance spacing over whole free spectral range based on Autler-Townes splitting in a single microring resonator.

In this paper, a single microring resonator structure formed by incorporating a reflectivity-tunable loop mirror is demonstrated for the tuning of resonance spacing. Autler-Townes splitting in the resonator is utilized to tune the spacing between two adjacent resonances by controlling the strength of coupling between the two counter-propagating degenerate modes in the microring resonator. A theoretical model based on the transfer matrix method is built to analyze the device. The theoretical analysis indicates that the resonance spacing can be tuned from zero to one free spectral range (FSR). In experiment, by integrating metallic microheater, the tuning of resonance spacing in the range of the whole FSR (1.17 nm) is achieved within 9.82 mW heating power dissipation. The device has potential for applications in reconfigurable optical filtering and microwave photonics.

Single germanium quantum dot embedded in photonic crystal nanocavity for light emitter on silicon chip.

A silicon light emitter in telecom-band based on a single germanium quantum dot precisely embedded in a silicon photonic crystal nanocavity is fabricated by a scalable method. A sharp resonant luminescence peak is observed at 1498.8 nm, which is enhanced by more than three orders of magnitude. The Purcell factor for the fundamental resonant mode is estimated from enhancement factor and increased collection efficiency. The cavity modes coupled to the ground state and excited state emission of germanium quantum dot are identified in the luminescence spectrum. Our devices provide a CMOS-compatible way of developing silicon-based low-power consuming light emitters, and are promising for realizing on-chip single photon sources.

Design of a femtogram scale double-slot photonic crystal optomechanical cavity.

We present the design of a double-slot photonic crystal cavity as an optomechanical device which contains a nanomechanical resonator with an effective mass as small as 6.91 fg. The optical Q-factor is optimized to 2 × 10(5). Using phononic crystals, the mechanical vibration is confined in a small volume to form a mechanical mode of 4 GHz with a high mechanical Q-factor and a femtogram effective mass. The localized mechanical mode overlaps with the optical field and strengthens the optomechanical coupling with a vacuum optomechanical coupling rate g0/2π exceeding 600 kHz. Considering fabrication imperfections, structures with deviation from ideal design are studied. The symmetry breakage of the structures and the displacement fields makes the mechanical effective masses reduced and close to 4 fg. The devices can be used in ultrasensitive sensing of mass, force and displacement.

Enhanced parametric frequency conversion in a compact silicon-graphene microring resonator.

We demonstrate four-wave mixing (FWM) in a 10-µm-radius silicon microring resonator with the assistance of giant nonlinearity of the monolayer graphene. A maximum enhancement of 6.8 dB of conversion efficiency in the silicon-graphene microring (SGM) resonator is observed. A nonlinear propagation model is established and the optical Kerr coefficient of the silicon-graphene hybrid waveguide is three times larger than that of the silicon waveguide.

Experimental demonstration of a microdisk resonator filter/buffer utilizing two-mode interference.

We have experimentally demonstrated a microdisk-resonator (MDR)-based filter for filtering and buffering applications utilizing two-mode interference. Optical filtering or buffering behavior can be generated by the coherent interference between two orthogonal whispering-gallery modes (WGMs) in a MDR symmetrically coupled to two bus waveguides. MDRs were fabricated using nanofabrication processes on a silicon-on-insulator platform. Multiple resonances of WGMs are excited in a MDR and unique filter characteristics have been observed for two spectrally nearby resonances. The measured results agree well with the theoretical simulation. Bandpass filtering is achieved with a 3 dB bandwidth of 0.66 nm and an in-band ripple of less than 1 dB when the two resonances are detuned, while the filter can function as an optical buffer with an insertion loss of 5.85 dB and a predicted time delay of 15 ps when the two resonances are approximately aligned. Furthermore, the influence of resonance spacing is analyzed on the performance of this filter.

Coherent interaction between two orthogonal travelling-wave modes in a microdonut resonator for filtering and buffering applications.

We theoretically investigate the coherent interaction between two orthogonal travelling-wave modes in a microdonut resonator symmetrically coupled to two bus waveguides. An analytical model has been developed to describe this structure using transfer matrix method. The simulation reveals that the two-mode microdonut can exhibit either a flat-top response or all-pass transmission, governed by the resonance spacing. Then, we implement analytical simulations to characterize the device and analyze the influence of coupling efficiencies and propagation losses of two resonant modes on behavior. Consequently, finite difference time domain simulations have been performed. The numerical results validate our theoretical analysis, and optical buffering effect is demonstrated in a pulse propagation simulation, when the two resonances are aligned. In addition, we show that the device function can be switched between flat-top filtering and all-pass filtering by tuning the local refractive index in a microdonut. Hence, this structure is promising for on-chip optical filtering and buffering applications.

High-speed silicon modulator with band equalization.

Electro-optic modulation up to 70 Gbit/s has been demonstrated using a silicon Mach-Zehnder modulator with a bias voltage of -1.5 V. In a wide frequency range from DC, an increasing input impedance of the modulator was designed to equalize its electro-optic frequency response. Without a bias voltage, the 3 dB bandwidth was measured as 35 GHz and it is predicted to be as high as 55 GHz at -3 V bias. Frequency responses of the modulator operated with counter-propagating waves were tested to verify the proposed prediction model.

Enhanced light emission from Ge quantum dots in photonic crystal ring resonator.

Light emitter based on Ge quantum dots embedded in photonic crystal ring resonator is designed and fabricated. Six sharp resonant peaks dominate the photoluminescence (PL) spectrum ranging from 1500 to 1600 nm at room temperature. The light emission enhancement is due to Purcell effect and high collection efficiency of the PCRR verified by calculated far-field patterns. The Purcell factor of the PCRR is estimated from enhancement factor and increased collection efficiency. The linewidth of the emission of a single Ge quantum dot is estimated from the Purcell factor.

High-quality-factor photonic crystal ring resonator.

A design for enhancing the quality (Q) factor of a photonic crystal ring resonator (PCRR) is introduced. The highest Q factor based on simulations is 121,000. The analysis of momentum space distributions of the electric field profile for PCRR resonance shows that a high Q factor of a PCRR is attributed to the reduction of tangential k-vector component inside the leaky region. A high Q factor of 75,200 is experimentally demonstrated for a modified PCRR on a silicon-on-insulator wafer. The high-Q-factor PCRR demonstrated here will be beneficial for channel drop filters, lasers, sensors, and other applications.

Silicon optical diode based on cascaded photonic crystal cavities.

An all-silicon passive optical diode based on optical nonlinearity in cascaded photonic crystal (PhC) L3 cavities is proposed and demonstrated. A nonreciprocal transmission ratio (NTR) of 30.8 dB and insertion loss of 8.3 dB are realized in the device. The device has a relatively broad 17 dB operation bandwidth of 0.08 nm, and at least 16 dB of NTR is achieved when input power varies between -6.25 and -2.95 dBm. A nonlinear couple mode model for cascaded PhC cavities is established to analyze the behavior of the device, and numerical simulation results are in good agreement with the experiment results.

Electromagnetically induced transparency-like effect in a two-bus waveguides coupled microdisk resonator.

We observe theoretically and experimentally electromagnetically induced transparency (EIT)-like effect in a single microdisk resonator (MDR) evanescently coupled with two bus waveguides. This structure is modeled using transfer matrix method, and it is revealed that the EIT-like spectrum originates from the coherent interference between two nearby low-order whispering-gallery modes (WGMs) with comparable quality factors. The EIT-like properties have been investigated analytically with respect to coupling efficiency, round-trip power attenuation, as well as phase spacing between two resonances. The resonance spacing and mode coupling are adjustable by varying the effective indices of WGMs and waveguide mode. Consequently, fully integrated MDRs were fabricated in silicon. Resonant modes and coupling efficiency are studied in one-bus waveguide coupled MDRs. Finally, EIT-like resonance is observed in a two-bus waveguides coupled MDR of 3 µm in radius with a quality factor of 4,200 and central transmission larger than 0.65. The experimental results agree with our modeling well and show good internal consistency, confirming that two WGMs coupled in a point-to-point manner are required for EIT-like effect.

Fast and efficient silicon thermo-optic switching based on reverse breakdown of pn junction.

We propose and demonstrate a fast and efficient silicon thermo-optic switch based on reverse breakdown of the pn junction. Benefiting from the direct heating of silicon waveguide by embedding the pn junction into the waveguide center, fast switching with on/off time of 330 and 450 ns and efficient thermal tuning of 0.12 nm/mW for a 20 µm radius microring resonator are achieved, indicating a high figure of merit of only 8.8 mW·µs. The results here show great potential for application in the future optical interconnects.

Germanium epitaxy on silicon.

With the rapid development of on-chip optical interconnects and optical computing in the past decade, silicon-based integrated devices for monolithic and hybrid optoelectronic integration have attracted wide attention. Due to its narrow pseudo-direct gap behavior and compatibility with Si technology, epitaxial Ge-on-Si has become a significant material for optoelectronic device applications. In this paper, we describe recent research progress on heteroepitaxy of Ge flat films and self-assembled Ge quantum dots on Si. For film growth, methods of strain modification and lattice mismatch relief are summarized, while for dot growth, key process parameters and their effects on the dot density, dot morphology and dot position are reviewed. The results indicate that epitaxial Ge-on-Si materials will play a bigger role in silicon photonics.

Compact and low-loss silicon power splitter based on inverse tapers.

A compact, low-loss, optical power splitter based on inverse tapers is proposed and fabricated on a silicon-on-insulator platform. High efficiency mode evolution between the fundamental mode of the input waveguide and the super mode of the output waveguides is realized using optimized tapers. A 1×4 splitter with insertion loss lower than 0.4 dB and uniformity better than 0.68 dB in a wavelength range from 1510 to 1550 nm are demonstrated within a footprint of only ~75 µm(2). These properties are very promising for ultrahigh density photonic integration applications.