The Crosstalk and Clinical Implications of CircRNAs and Glucose Metabolism in Gastrointestinal Cancers.

The majority of glucose in tumor cells is converted to lactate despite the presence of sufficient oxygen and functional mitochondria, a phenomenon known as the "Warburg effect" or "aerobic glycolysis". Aerobic glycolysis supplies large amounts of ATP, raw material for macromolecule synthesis, and also lactate, thereby contributing to cancer progression and immunosuppression. Increased aerobic glycolysis has been identified as a key hallmark of cancer.

Circ_CEA promotes the interaction between the p53 and cyclin-dependent kinases 1 as a scaffold to inhibit the apoptosis of gastric cancer.

Circular RNAs (circRNAs) have been reported to play essential roles in tumorigenesis and progression. This study aimed to identify dysregulated circRNAs in gastric cancer (GC) and investigate the functions and underlying mechanism of these circRNAs in GC development. Here, we identify circ_CEA, a circRNA derived from the back-splicing of CEA cell adhesion molecule 5 (CEA) gene, as a novel oncogenic driver of GC.

PAD4-dependent citrullination of nuclear translocation of GSK3β promotes colorectal cancer progression via the degradation of nuclear CDKN1A.

Peptidylarginine deiminase 4 (PAD4), a Ca-dependent enzyme, catalyzes the conversion of arginine to citrulline and has been strongly associated with many malignant tumors. However, the molecular mechanisms of PAD4 in the development and progression of colorectal cancer (CRC) remain unclearly defined. In our study, PAD4 expression was increased in CRC tissues and cells, and was closely related to tumor size, lymph node metastasis.

Vimentin binds to a novel tumor suppressor protein, GSPT1-238aa, encoded by circGSPT1 with a selective encoding priority to halt autophagy in gastric carcinoma.

Circular RNAs (circRNAs) are covalently closed, endogenous molecules that are widespread in eukaryotes. Recent evidence indicates that circRNAs play important roles in carcinogenesis. Several circRNAs have been reported to comprise translatable RNA; however, whether circRNAs encode functional proteins remains unknown.

Identification of an IRES within the coding region of the structural protein of human rhinovirus 16.

As an alternative mechanism for cap-dependent (m7GpppN) translation, internal ribosome entry site (IRES)-dependent translation has been observed in the 5' untranslated regions (5' UTR) and coding regions of a number of viral and eukaryotic mRNAs. In this study, a series of 5' terminal truncated structural protein genes that were fused with GFP was used to screen for potential IRESs, and IRESs were identified using a bicistronic luciferase vector or GFP expression vector possessing a hairpin structure. Our results revealed that a putative IRES was located between nt 1982 and 2281 in the VP3 coding region of the human rhinovirus 16 (HRV16) genomes.

A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression.

Background: Circular RNA (circRNA), a subclass of non-coding RNA, plays a critical role in cancer tumorigenesis and metastasis. It has been suggested that circRNA acts as a microRNA sponge or a scaffold to interact with protein complexes; however, its full range of functions remains elusive. Recently, some circRNAs have been found to have coding potential.

Identification of cryptic putative IRESs within the ORF encoding the nonstructural proteins of the human rhinovirus 16 genome.

Internal ribosome entry site (IRES)-dependent translation is a mechanism distinct from 5' cap-dependent translation. IRES elements are located mainly in the 5' untranslated regions (UTRs) of viral and eukaryotic mRNAs. However, IRESs are also found in the coding regions of some viral and eukaryotic genomes to initiate the translation of some functional truncated isoforms.

Non-Structural Protein 2B of Human Rhinovirus 16 Activates Both PERK and ATF6 Rather Than IRE1 to Trigger ER Stress.

To understand the underlying mechanisms of endoplasmic reticulum (ER) stress caused by human rhinovirus (HRV) 16 and non-structural transmembrane protein 2B, the expressions of ER chaperone glucose-regulated protein 78 (GRP78) and three signal transduction pathways, including protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1 (IRE1), were evaluated after HRV16 infection and 2B gene transfection. Our results showed that both HRV16 infection and 2B gene transfection increased the expression of ER chaperone GRP78, and induced phosphorylation of PERK and cleavage of ATF6 in a time-dependent manner. Our data also revealed that the HRV16 2B protein was localized to the ER membrane.

Identification of the internal ribosome entry sites (IRES) of prion protein gene.

Many studies demonstrated that there are several type bands of prion protein in cells. However, the formation of different prion protein bands is elusive. After several low molecular weight bands of prion protein appeared in SMB-S15 cells infected with scrapie agent Chandler, we think that IRES-dependent translation mechanism induced by prion is involved in the formation of prion protein bands.

Coxsackievirus B3 2A protease promotes encephalomyocarditis virus replication.

To determine whether 2A protease of the enterovirus genus with type I internal ribosome entry site (IRES) effect on the viral replication of type II IRES, coxsackievirus B3(CVB3)-encoded protease 2A and encephalomyocarditis virus (EMCV) IRES (Type II)-dependent or cap-dependent report gene were transiently co-expressed in eukaryotic cells. We found that CVB3 2A protease not only inhibited translation of cap-dependent reporter genes through the cleavage of eIF4GI, but also conferred high EMCV IRES-dependent translation ability and promoted EMCV replication. Moreover, deletions of short motif (aa13-18 RVVNRH, aa65-70 KNKHYP, or aa88-93 PRRYQSH) resembling the nuclear localization signals (NLS) or COOH-terminal acidic amino acid motif (aa133-147 DIRDLLWLEDDAMEQ) of CVB3 2A protease decreased both its EMCV IRES-dependent translation efficiency and destroy its cleavage on eukaryotic initiation factor 4G (eIF4G) I.