The emerging role of m6A modification of non-coding RNA in gastrointestinal cancers: a comprehensive review

Gastrointestinal (GI) cancer is a series of malignant tumors with a high incidence globally. Although approaches for tumor diagnosis and therapy have advanced substantially, the mechanisms underlying the occurrence and progression of GI cancer are still unclear. Increasing evidence supports an important role for N6-methyladenosine (m6A) modification in many biological processes, including cancer-related processes via splicing, export, degradation, and translation of mRNAs. Under distinct cancer contexts, m6A regulators have different expression patterns and can regulate or be regulated by mRNAs and non-coding RNAs, especially long non-coding RNAs. The roles of m6A in cancer development have attracted increasing attention in epigenetics research. In this review, we synthesize progress in our understanding of m6A and its roles in GI cancer, especially esophageal, gastric, and colorectal cancers. Furthermore, we clarify the mechanism by which m6A contributes to GI cancer, providing a basis for the development of diagnostic, prognostic, and therapeutic targets

Data and Knowledge Co-driving for Cancer Subtype Classification on Multi-Scale Histopathological Slides

Artificial intelligence-enabled histopathological data analysis has become a valuable assistant to the pathologist. However, existing models lack representation and inference abilities compared with those of pathologists, especially in cancer subtype diagnosis, which is unconvincing in clinical practice. For instance, pathologists typically observe the lesions of a slide from global to local, and then can give a diagnosis based on their knowledge and experience. In this paper, we propose a Data and Knowledge Co-driving (D&K) model to replicate the process of cancer subtype classification on a histopathological slide like a pathologist. Specifically, in the data-driven module, the bagging mechanism in ensemble learning is leveraged to integrate the histological features from various bags extracted by the embedding representation unit. Furthermore, a knowledge-driven module is established based on the Gestalt principle in psychology to build the three-dimensional (3D) expert knowledge space and map histological features into this space for metric. Then, the diagnosis can be made according to the Euclidean distance between them. Extensive experimental results on both public and in-house datasets demonstrate that the D&K model has a high performance and credible results compared with the state-of-the-art methods for diagnosing histopathological subtypes. Code: https://github.com/Dennis-YB/Data-and-Knowledge-Co-driving-for-Cancer-Subtypes-Classificatio

IRES-Mediated Protein Translation Overcomes Suppression by the p14ARF Tumor Suppressor Protein.

Internal ribosome entry sites (IRES elements) have attracted interest in cancer gene therapy because they can be used in the design of gene transfer vectors that provide bicistronic co-expression of two transgene products under the control of a single promoter. Unlike cellular translation of most mRNAs, a process that requires a post-translational 5' modification of the mRNA known as the cap structure, IRES-mediated translation is independent of the cap structure. The cellular conditions that may intervene to modulate IRES-mediated, cap-independent versus cap-dependent translation, however, remain poorly understood, although they could be critical to the choice of gene transfer vectors. Here we have compared the effects of the p14ARF (Alternate Reading Frame) tumor suppressor, a translational suppressor frequently overexpressed in cancer, on cap-dependent translation versus cap-independent translation from the EMCV viral IRES often used in bicistronic gene transfer vectors. We find that ectopic overexpression of p14ARF suppresses endogenous and ectopic cap-dependent protein translation, consistent with other studies. However, p14ARF has little or no effect on transgene translation initiated within an IRES element. This suggests that transgenes placed downstream of an IRES element will retain efficient translation of their gene products in the presence of high levels of ectopic or endogenous p14ARF, a finding that could be particularly relevant to therapeutic gene therapy strategies for cancer

Dual CP Polarization Diversity and Space Diversity Antennas Enabled by a Compact T-Shaped Feed Structure

A compact T-shaped feed structure (IFS) is reported that enables the realization of two types of diversity antennas: a polarization diversity antenna (PDA) and a spatial diversity antenna (SDA). Both systems have a high potential for mobile wireless communication applications. The IFS includes four ports and two independent coaxial channels with effective isolation between them all. The PDA is a dual CP omnidirectional antenna. Its optimized prototype achieves measured impedance bandwidths of 16.4% and 15.28% in its LHCP and RHCP states, respectively, and realized gains in both between 4.8 and 6.46 dBic. The inner thin coaxial cable (ITCC) of the TFS directly drives its LHCP subsystem, facilitating its improved omnidirectional performance. This ITCC is also used to directly feed the SDA's low-profile directional planar equiangular spiral antenna and its side port drives its omnidirectional RHCP antenna. Good hemispherical coverage is realized with a measured common impedance bandwidth larger than 14.35% with more than 40-dB isolation between its two ports. The corresponding measured realized gain of the SDA is between 4 and 7.8 dBic. The measured results for both optimized prototypes confirm their simulated performance characteristics.National Natural Science Foundation [61571289, 61571298, 61701303]; Natural Science Foundation of Shanghai [17ZR1414300]; Shanghai Pujiang Program [17PJ1404100]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the <it>MDR1 </it>gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the <it>MDR1 </it>gene. Overexpression of <it>MDR1 </it>gene has often been reported in primary gastric adenocarcinoma.</p> <p>Methods</p> <p>This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining.</p> <p>Results</p> <p>The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (<it>MDR1</it>) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and <it>MDR1 </it>expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy.</p> <p>Conclusion</p> <p>Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line.</p