Targeting LINC070974 inhibits lung adenocarcinoma cell proliferation and progression by interacting with Y-box binding protein 1.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Increasing evidence suggests that long noncoding RNAs play crucial roles in lung cancer pathogenesis. We previously identified a novel lncRNA, LINC070974, which is associated with tumor cell proliferation. In the present study, we find that knockdown of LINC070974 inhibits cell proliferation, migration and invasion as well as tumor formation both in vitro and in nude mice. LINC070974 silencing also improves cisplatin efficacy in A549/DDP cells. The function of LINC070974 may depend on its interaction with YBX1. Knockdown of LINC070974 reduces the recruitment of YBX1 to the CCND1 promoter and delays tumor progression through its coregulatory genes, which are mainly involved in the p53 signaling pathway. We utilize nebulized inhalation to deliver siRNAs targeting LINC070974 and find that LINC070974 significantly prevents tumor metastasis and growth in lung tissues. These findings reveal the role of LINC070974 in lung cancer and suggest a promising therapeutic approach involving siRNA inhalation.

LncRP11-675F6.3 responds to rapamycin treatment and reduces triglyceride accumulation via interacting with HK1 in hepatocytes by regulating autophagy and VLDL-related proteins.

Long noncoding RNAs (lncRNAs) have been widely proven to be involved in liver lipid homeostasis. Herein, we identify an upregulated lncRNA named lncRP11-675F6.3 in response to rapamycin treatment using a microarray in HepG2 cells. Knockdown of lncRP11-675F6. 3 leads to a significant reduction in apolipoprotein 100 (ApoB100), microsomal triglyceride transfer protein (MTTP), ApoE and ApoC3 with increased cellular triglyceride level and autophagy. Furthermore, we find that ApoB100 is obviously colocalized with GFP-LC3 in autophagosomes when lncRP11-675F6. 3 is knocked down, indicating that elevated triglyceride accumulation likely related to autophagy induces the degradation of ApoB100 and impairs very low-density lipoprotein (VLDL) assembly. We then identify and validate that hexokinase 1 (HK1) acts as the binding protein of lncRP11-675F6.3 and mediates triglyceride regulation and cell autophagy. More importantly, we find that lncRP11-675F6.3 and HK1 attenuate high fat diet induced nonalcoholic fatty liver disease (NAFLD) by regulating VLDL-related proteins and autophagy. In conclusion, this study reveals that lncRP11-675F6.3 is potentially involved in the downstream of mTOR signaling pathway and the regulatory network of hepatic triglyceride metabolism in cooperation with its interacting protein HK1, which may provide a new target for fatty liver disorder treatment.

LncNONMMUG027912 alleviates lipid accumulation through AMPKα/mTOR/SREBP1C axis in nonalcoholic fatty liver.

Various metabolic diseases are closely related to lipid metabolism disorders, but the regulatory effect of long noncoding RNAs (lncRNAs) on the function of lipids has been poorly elucidated. Previous our work has found that lncNONMMUG027912 (abbreviated as lnc027912) involved in cholesterol metabolism. Here, we further explored the novel function of lipid metabolism-associated lnc027912. We found that upregulated lnc027912 in AML12 cells treated with oleic acid (OA) and palmitic acid (PA) showed a significant decrease in lipid accumulation, triglyceride (TG) levels, and lipid biosynthesis genes. In terms of regulatory mechanisms, lnc027912 increased the expression of p-AMPKα, inhibited p-mTOR levels, decreased the expression of SREBP1C in nuclei, decreased the promoter activity of SREBP1C, and inhibited the expression of lipid synthesis genes. Most importantly, lnc027912 could reduce lipid accumulation and liver inflammation through AMPKα/mTOR signal axis in nonalcoholic fatty liver disease (NAFLD) mice model. Altogether, our study revealed a novel molecular mechanism of lnc027912 in lipid metabolism through the AMPKα/mTOR/SREBP1C signaling axis and highlights the potential of lnc027912 as a new treatment target for lipid disorder diseases (such as NAFLD).

Algorithm-Assisted Detection and Imaging of microRNAs in Living Cancer Cells via the Disassembly of Plasmonic Core-Satellite Probes Coupled with Strand Displacement Amplification.

Acute detection and high-resolution imaging of microRNAs (miRNAs) in living cancer cells have attracted great attention in clinical diagnosis and therapy. However, current methods suffer from low detection sensitivity or heavy dependence on expensive and sophisticated spectrometers. Herein, a novel algorithm-assisted system of detecting and imaging miRNAs in living cancer cells was developed via the disassembly of plasmonic core-satellite probes coupled with strand displacement amplification (SDA). The target miRNAs in the system could trigger the disassembly of plasmonic core-satellite probes, leading to the color change in the scattering light of the probes, which could be captured by dark-field microscopy (DFM). The concentration of the target miRNAs was obtained by analyzing the dark-field image based on the proposed algorithm with a detection limit of 2 pM for miRNA-21. Thus, the performance in terms of simplicity and sensitivity of the system compared with one of the conventional spectrophotometers was well presented, which could inspire more clinical applications of inexpensive, intelligent, and rapid screening of cancer cells. The application software based on the proposed algorithm running on the Android platform was also developed, demonstrating the potential of remote diagnosis.

Establishment of a universal and sensitive plasmonic biosensor platform based on the hybridization chain reaction (HCR) amplification induced by a triple-helix molecular switch.

Herein, we established a universal and sensitive plasmonic sensing strategy for biomolecule assays by coupling the hybridization chain reaction (HCR) strategy and a triple-helix molecular switch. Upon the recognition of the target, a single-stranded DNA as a universal trigger (UT) was released from the triple-helix molecular switch (THMS). Thus, the HCR process can be triggered between two hairpins M1 and M2, resulting in the aggregation of gold nanoparticles (AuNPs) via the hybridization between the tail sequence on M1 (or M2) and a DNA-AuNP probe with a dramatic change in the absorbance at 521 nm. More specifically, the strategy, which was conducted by the introduction of target-specific recognition of THMS and universalized by virtue of altering the aptamer or DNA sequence without changing the triple-helix structure, enables simple design for multiple target detection. By taking advantage of THMS, this strategy could enable stable and sensitive detection of a variety of targets including nucleic acids, small molecules and proteins, which may possess great potential for practical applications.

ROS-augmented and tumor-microenvironment responsive biodegradable nanoplatform for enhancing chemo-sonodynamic therapy.

Nanocarrier for augmenting the efficacy of reactive oxygen species (ROS) by tumor microenvironment (TME) has become an emerging strategy for cancer treatment. Herein, a smart biodegradable drug delivery nanoplatform with mitochondrial-targeted ability, pH-responsive drug release and enzyme-like catalytic function is designed. This efficient ROS-generating platform uses ultrasound with deeper penetration capability as excitation source for combined chemotherapy and sonodynamic therapy (SDT) of tumor. In vitro experiments show that the nanoplatform can co-load Ce6 and DOX and be degraded in slight acid environment, and the DOX release rate is 63.91 ± 1.67%. In vivo experiments show that the nanoplatform has extremely biosafety and can be enriched in tumor site and excluded from body after 24 h. More significantly, after combined treatment, the tumors are eliminated and the mice still survive healthily without recurrence after 60 d. This is because not only it can achieve mitochondrial targeting and use platinum particle to increase oxygen content in TME to enhance the effect of SDT, but also it can use weak acidic TME to accelerate drug release to achieve the combination of chemotherapy and SDT. The probe provides a new strategy for designing ROS-based nanoplatform for the treatment of malignant tumor.

A versatile dynamic light scattering strategy for the sensitive detection of microRNAs based on plasmonic core-satellites nanoassembly coupled with strand displacement reaction.

A low-cost, effective and enzyme-free sensing strategy for ultrasensitive microRNA (miRNA) detection was developed based on dynamic light scattering (DLS) coupled with strand displacement reaction (SDR). The combination of DLS and SDR was used to assess the size changes of core-satellites nanoassembly. This strategy realized the limit of detection (LOD) as low as 0.24 pM (S/N = 3) and the detection range of 5 pM-150 pM, which might urge this strategy as an ideal candidate for the sensitive detection of miRNA in the future. In addition, the proposed strategy could be successfully used to analyze target miRNA in various cancer cells, indicating that the developed SDR-DLS strategy has promising clinical implications for rapid and early diagnosis of cancer-related diseases.

Logic Sensing of MicroRNA in Living Cells Using DNA-Programmed Nanoparticle Network with High Signal Gain.

Molecular circuits capable of implementing Boolean logic in cellular environments have emerged as an important tool for in situ sensing, elucidating, and modulating cell functions. The performance of existing molecular computation devices in living cells is limited because of the low level of biomolecular inputs and moderate signal gain. Herein, we devised a new class of DNA-programmed nanoparticle network with integrated molecular computation and signal amplification functions for logic sensing of dual microRNA (miRNA) molecules in living cells. The nanoparticle network, which is composed of DNA-bridged gold nanoparticles and quantum dots (QDs), could simultaneously interface with two miRNA molecules, amplify the molecular inputs, perform a calculation through AND logic gate, and generate QD photoluminescence (PL) as an output signal. Significant improvement in imaging sensitivity is achieved by integrating the signal amplifier into the molecular computation device. It allows discrimination of specific cancer cell types via intelligent sensing of miRNA patterns in living cells.

DNA-templated nanoparticle complexes for photothermal imaging and labeling of cancer cells.

In situ monitoring of the photothermal (PT) effect at the cellular level is of great importance in the photothermal (PT) treatment of cancer. Herein, we report a class of DNA-templated gold nanoparticle (GNP)-quantum dot (QD) complexes (GQC) for PT sensing in solution and in cancer cells in vitro. Specifically, the QD photoluminescence (PL) could be activated at elevated temperature with a wide thermo-responsive range between 45 °C and 70 °C, which fits the temperature threshold for effective cancer cell ablation. The general applicability of GQC for intracellular PT sensing is explored using three types of PT agents (gold nanorods (GNRs), gold nanostars (GNSs), and Prussian blue nanoparticles (PBNPs)) with various PT performances. We show that the intracellular QD PL is gradually activated with increasing near-infrared (NIR) irradiation time, providing a good correlation with the surrounding medium temperature for PT sensing. Moreover, we demonstrate that the GQC sensor could be used for specific photothermal labeling and imaging of cancer cells. The QD PL signal is retained in the cells post-treatment, thereby potentially enabling persistent photothermal labeling of cancer cells for post-treatment cell tracking and imaging-guided therapy evaluation.

Photocaged Nanoparticle Sensor for Sensitive MicroRNA Imaging in Living Cancer Cells with Temporal Control.

Sensitive imaging of microRNA in living cells is of great value for disease diagnostics and prognostics. While signal amplification-based strategies have been developed for imaging low-abundance disease-relevant microRNA molecules, precise temporal control over sensor activity in living cells still remains a challenge, and limits their applications for sensing microRNA concentration dynamics. Herein, we report a class of photocaged nanoparticle sensors for highly sensitive imaging of microRNA in living cells with temporal control. The sensor features a DNA-templated gold nanoparticle-quantum dot satellite nanostructure which is temporarily inactivated by a photocaged DNA mask. Upon UV light irradiation, the sensor restores its activity for catalytic sensing of microRNA in living cells via entropy-driven two-step toehold-mediated strand displacement reactions. We show that the sensor exhibits quick response to UV light, robust intracellular stability, and high specificity and sensitivity for the microRNA target. On the basis of this strategy, precise control over sensor activity is achieved using an external light trigger, where on-demand sensing could be potentially performed with spatiotemporal control.

Next-Generation DNA-Functionalized Quantum Dots as Biological Sensors.

DNA-functionalized quantum dots (DNA-QDs) have found considerable application in biosensing and bioimaging. Different from the first generation (I-G) DNA-QDs prepared via conventional bioconjugation chemistry, the second generation (II-G) DNA-QDs prepared via one-step DNA-templated QD synthesis features a defined number of DNA valencies (usually monovalency), which is preferable for controlled assembly and biological targeting. In this review, we summarize recent progress in designing QD probes based on II-G DNA-QDs for advanced sensing and imaging applications. It opens up new avenues for highly sensitive and intelligent sensing of a range of disease-relevant biomolecules in vitro and in living cells.

MicroRNA-Catalyzed Cancer Therapeutics Based on DNA-Programmed Nanoparticle Complex.

The use of cancer-relevant microRNA molecules as endogenous drug release stimuli is promising for personalized cancer treatment yet remains a great challenge because of their low abundance. Herein, we report a new type of microRNA-catalyzed drug release system based on DNA-programmed gold nanoparticle (GNP)-quantum dot (QD) complex. We show that a trace amount of miRNA-21 molecules could specifically catalyze the disassembly of doxorubicin (Dox)-loaded GNP-QDs complex through entropy driven process, during which the Dox-intercalating sites are destructed for drug release. This catalytic reaction could proceed both in fixed cells and live cells with miRNA-21 overexpression. Dox molecules could be efficiently released in the cells and translocate to cell nuclei. QD photoluminescence is simultaneously activated during catalytic disassembly process, thus providing a reliable feedback for microRNA-triggered drug release. The GNP-QDs-Dox complex exhibits much higher drug potency than free Dox molecules, and therefore represents a promising platform for accurate and effective cancer cell treatment.

Catalytic Molecular Imaging of MicroRNA in Living Cells by DNA-Programmed Nanoparticle Disassembly.

Molecular imaging is an essential tool for disease diagnostics and treatment. Direct imaging of low-abundance nucleic acids in living cells remains challenging because of the relatively low sensitivity and insufficient signal-to-background ratio of conventional molecular imaging probes. Herein, we report a class of DNA-templated gold nanoparticle (GNP)-quantum dot (QD) assembly-based probes for catalytic imaging of cancer-related microRNAs (miRNA) in living cells with signal amplification capacity. We show that a single miRNA molecule could catalyze the disassembly of multiple QDs with the GNP through a DNA-programmed thermodynamically driven entropy gain process, yielding significantly amplified QD photoluminescence (PL) for miRNA imaging. By combining the robust PL of QDs with the catalytic amplification strategy, three orders of magnitude improvement in detection sensitivity is achieved in comparison with non-catalytic imaging probe, which enables facile and accurate differentiation between cancer cells and normal cells by miRNA imaging in living cells.

[A discussion on the biological evaluation method for nanosilver antibiotic devices for gynecological external use].

Nanosilver antibiotic devices for gynecological external use are the third-class products of medical devices, whose biological safety and efficiency should be strictly controlled. But there is not yet the national standard or industry standard for the products to control the production process, so their testing method of biological evaluation mainly refers to GB/T16886 "The Guide to Implementation of Biological Evaluation of Medical Devices". To control the biological safety effectively, it's necessary to work out the testing items and methods of the biological evaluation for such products.