Circular RNAs (CircRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitous across species ranging from viruses to mammals. Important advances have been made in the biogenesis, ...regulation, localization, degradation and modification of circRNAs. CircRNAs exert biological functions by acting as transcriptional regulators, microRNA (miR) sponges and protein templates. Moreover, emerging evidence has revealed that a group of circRNAs can serve as protein decoys, scaffolds and recruiters. However, the existing research on circRNA-protein interactions is quite limited. Hence, in this review, we briefly summarize recent progress in the metabolism and functions of circRNAs and elaborately discuss the patterns of circRNA-protein interactions, including altering interactions between proteins, tethering or sequestering proteins, recruiting proteins to chromatin, forming circRNA-protein-mRNA ternary complexes and translocating or redistributing proteins. Many discoveries have revealed that circRNAs have unique expression signatures and play crucial roles in a variety of diseases, enabling them to potentially act as diagnostic biomarkers and therapeutic targets. This review systematically evaluates the roles and mechanisms of circRNAs, with the hope of advancing translational medicine involving circRNAs.
Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) ...progression and could be a potential therapeutic target.
We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with LINRIS inhibited were tested in vitro and in vivo.
LINRIS was upregulated in CRC tissues from patients with poor overall survival (OS), and LINRIS inhibition led to the impaired CRC cell line growth. Moreover, knockdown of LINRIS resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N
-methyladenosine (m
A) 'reader'. LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of LINRIS attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of LINRIS could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of LINRIS suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models.
LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.
ObjectiveTo monitor trastuzumab resistance and determine the underlying mechanisms for the limited response rate and rapid emergence of resistance of HER2+ metastatic gastric cancer ...(mGC).DesignTargeted sequencing of 416 clinically relevant genes was performed in 78 paired plasma and tissue biopsy samples to determine plasma-tissue concordance. Then, we performed longitudinal analyses of 97 serial plasma samples collected from 24 patients who were HER2+ to track the resistance during trastuzumab treatment and validated the identified candidate resistance genes.ResultsThe results from targeted sequencing-based detection of somatic copy number alterations (SCNA) of HER2 gene were highly consistent with fluorescence in situ hybridisation data, and the detected HER2 SCNA was better than plasma carcinoembryonic antigen levels at predicting tumour shrinkage and progression. Furthermore, most patients with innate trastuzumab resistance presented high HER2 SCNA during progression compared with baseline, while HER2 SCNA decreased in patients with acquired resistance. PIK3CA mutations were significantly enriched in patients with innate resistance, and ERBB2/4 genes were the most mutated genes, accounting for trastuzumab resistance in six (35.3%) and five (29.4%) patients in baseline and progression plasma, respectively. Patients with PIK3CA/R1/C3 or ERBB2/4 mutations in the baseline plasma had significantly worse progression-free survival. Additionally, mutations in NF1 contributed to trastuzumab resistance, which was further confirmed through in vitro and in vivo studies, while combined HER2 and MEK/ERK blockade overcame trastuzumab resistance.ConclusionLongitudinal circulating tumour DNA sequencing provides novel insights into gene alterations underlying trastuzumab resistance in HER2+mGC.
Irinotecan is one of the main chemotherapeutic agents for colorectal cancer (CRC). MicroRNA‐200 (miR‐200) has been reported to inhibit metastasis in cancer cells. Herein, pH‐sensitive and ...peptide‐modified liposomes and solid lipid nanoparticles (SLN) are designed for encapsulation of irinotecan and miR‐200, respectively. These peptides include one cell‐penetrating peptide, one ligand targeted to tumor neovasculature undergoing angiogenesis, and one mitochondria‐targeting peptide. The peptide‐modified nanoparticles are further coated with a pH‐sensitive PEG‐lipid derivative with an imine bond. These specially‐designed nanoparticles exhibit pH‐responsive release, internalization, and intracellular distribution in acidic pH of colon cancer HCT116 cells. These nanoparticles display low toxicity to blood and noncancerous intestinal cells. Delivery of miR‐200 by SLN further increases the cytotoxicity of irinotecan‐loaded liposomes against CRC cells by triggering apoptosis and suppressing RAS/β‐catenin/ZEB/multiple drug resistance (MDR) pathways. Using CRC‐bearing mice, the in vivo results further indicate that irinotecan and miR‐200 in pH‐responsive targeting nanoparticles exhibit positive therapeutic outcomes by inhibiting colorectal tumor growth and reducing systemic toxicity. Overall, successful delivery of miR and chemotherapy by multifunctional nanoparticles may modulate β‐catenin/MDR/apoptosis/metastasis signaling pathways and induce programmed cancer cell death. Thus, these pH‐responsive targeting nanoparticles may provide a potential regimen for effective treatment of colorectal cancer.
Collectively, successful delivery of miR and chemotherapy by pH‐responsive targeting nanoparticles modulates β‐catenin/multiple drug resistance/apoptosis/metastasis pathways and induces cancer cell death, mainly via apoptosis. These pH‐sensitive targeting nanoparticles carrying chemotherapy and gene therapeutics remarkably enhance anticancer efficacy in tumor‐bearing mice. Thus, these nanoparticles may provide a potential regimen for effective treatment of colorectal cancer.
Nuclear safety-related underground liquid storage tanks, such as those used to store fuel for emergency diesel generators, are critical components for safety of hundreds of existing nuclear power ...plants (NPP) worldwide. Since most of those NPP will continue to operate for decades, a beyond design base (BDB) seismic screening of safety-related underground tanks in those NPP is beneficial and essential to public safety. The analytical methodology for buried tank subjected to seismic effect, including a BDB seismic evaluation, needs to consider both soil-structure and fluid-structure interaction effects. Comprehensive analysis of such a soil-structure-fluid system is costly and time consuming, often subjected to availability of state-of-art finite element tools. Simple, but practically and reasonably accurate techniques for seismic evaluation of underground liquid storage tanks have not been established. In this study, a mechanics based solution is proposed for the evaluation of a cylindrical underground liquid storage tank using hand calculation methods. For validation, a practical example of two underground diesel fuel tanks in an existing nuclear power plant is presented and application of the proposed method is confirmed by using published results of the computer-aided System for Analysis of Soil Structural Interaction (SASSI). The proposed approach provides an easy to use tool for BDB seismic assessment prior to making decision of applying more costly technique by owner of the nuclear facility.
Tumor cells often reprogram their metabolism for rapid proliferation. The roles of long noncoding RNAs (lncRNAs) in metabolism remodeling and the underlying mechanisms remain elusive. Through ...screening, we found that the lncRNA Actin Gamma 1 Pseudogene (AGPG) is required for increased glycolysis activity and cell proliferation in esophageal squamous cell carcinoma (ESCC). Mechanistically, AGPG binds to and stabilizes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). By preventing APC/C-mediated ubiquitination, AGPG protects PFKFB3 from proteasomal degradation, leading to the accumulation of PFKFB3 in cancer cells, which subsequently activates glycolytic flux and promotes cell cycle progression. AGPG is also a transcriptional target of p53; loss or mutation of TP53 triggers the marked upregulation of AGPG. Notably, inhibiting AGPG dramatically impaired tumor growth in patient-derived xenograft (PDX) models. Clinically, AGPG is highly expressed in many cancers, and high AGPG expression levels are correlated with poor prognosis, suggesting that AGPG is a potential biomarker and cancer therapeutic target.
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines ...for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.
A novel linear polarization converter operating in C- and X-bands with high polarization conversion ratio is described and demonstrated based on frequency selective surface. The building element is a ...planar-dipole pair, which is orthogonally printed on a double-layer substrate and vertically connected by a pair of through-via holes functioning as a quasi-two-wire transmission line coupler. A perforated metal shielding layer is sandwiched between the double-layer structure to only support a transverse electric and magnetic (TEM) mode coupling between the top and bottom dipolar components. The front dipole responds to the incident transverse electric (TE) wave, and sends the induced current into the two-wire transmission line to feed the bottom dipole. The bottom dipole is orthogonal or oriented at an arbitrary angle with respect to the top one, and a resultant outgoing transverse magnetic (TM) wave or arbitrary orientation polarized wave can be achieved. In addition, a bidirectional orthogonal polarization converter is realized by using double orthogonally arranged planar-dipole pairs, which are also printed on the same double-layer substrate.
Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, which makes the prognostic prediction challenging. Ferroptosis, an iron-dependent form of regulated cell death, can be induced by ...sorafenib. However, the prognostic value of ferroptosis-related genes in HCC remains to be further elucidated. In this study, the mRNA expression profiles and corresponding clinical data of HCC patients were downloaded from public databases. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature in the TCGA cohort. HCC patients from the ICGC cohort were used for validation. Our results showed that most of the ferroptosis-related genes (81.7%) were differentially expressed between HCC and adjacent normal tissues in the TCGA cohort. Twenty-six differentially expressed genes (DEGs) were correlated with overall survival (OS) in the univariate Cox regression analysis (all adjusted
< 0.05). A 10-gene signature was constructed to stratify patients into two risk groups. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group (
< 0.001 in the TCGA cohort and
= 0.001 in the ICGC cohort). The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR> 1,
< 0.01). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups. In conclusion, a novel ferroptosis-related gene signature can be used for prognostic prediction in HCC. Targeting ferroptosis may be a therapeutic alternative for HCC.
2D perovskites have been considered as promising candidates for optoelectronic devices due to their good optical and electronic properties compared to 3D perovskites with significantly higher ...stability. Considering the commercial applications involving displays, image sensors, and fluorescent anti‐counterfeiting labels, the patterning technique of 2D perovskites is urgently required. However, existing patterning approaches still have challenges in high‐resolution fabrication. Here, a facile femtosecond laser direct writing method to fabricate arbitrarily patterned 2D perovskite films with well‐defined profiles and uniform fluorescence properties is developed. The flexible, fine, and non‐thermal diffused patterning abilities of femtosecond laser facilitate diverse 2D perovskite patterns exhibiting bright emission without any pinholes and cracks, as well as high resolution of approximate 2 µm line width. Based on this efficient patterning technique, this study demonstrates fluorescent anti‐counterfeiting labels (quick response code embedded with microlines) based on 2D perovskite films with high humidity stability, which can be identified from 43% to 96% relative humidity. This high‐resolution, reliable, efficient, and facile patterning technique for 2D perovskites with high humidity stability provides a promising technical route for 2D perovskite‐based optoelectronic applications.
For practical applications of 2D perovskites, a femtosecond laser direct writing method for patterning of 2D perovskites is proposed. Benefiting from the flexible, fine, and non‐thermal diffused patterning capabilities of a femtosecond laser, diverse 2D perovskite patterns exhibit bright and uniform emission properties without any pinholes and cracks and a high resolution of approximate 2 µm line width.
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