Riberborg3942

Circular RNA (circRNA/circ)‑ubiquitin associated protein 2 (UBAP2), a newly recognized circRNA, serves a functional role in several types of tumor, including ovarian cancer, colorectal cancer and osteosarcoma. However, the precise roles and molecular mechanism underlying circUBAP2 in osteosarcoma (OS) are not completely understood. In the present study, the expression levels of circUBAP2, microRNA (miR)‑204‑3p and (HMGA2) were evaluated via reverse transcription‑quantitative PCR in OS tissues and cells. Gambogic OS cell proliferation, migration, invasion and apoptosis were assessed by performing Cell Counting Kit‑8, Transwell and flow cytometry assays, respectively. HMGA2 protein expression levels were determined via western blotting. Dual‑luciferase reporter assays were performed to verify the interaction between circUBAP2 and miR‑204‑3p, and between miR‑204‑3p and HMGA2. An RNA immunoprecipitation (RIP) assay was conducted to confirm the interaction between circUBAP2 and miR‑204‑3p. The results demonstrated that cirso identified as one of the direct targets of HMGA2. Collectively, the results indicated that compared with the si‑NC group, circUBAP2 knockdown significantly inhibited OS cell malignant behavior by binding to miR‑204‑3p, which subsequently regulated HMGA2 expression. Therefore, the present study demonstrated that circUBAP2 expression was upregulated in OS, and circUBAP2 regulated OS cell malignant behavior via the miR‑204‑3p/HMGA2 axis.Circular RNA (circRNA) is a long non‑coding RNA molecule with a closed loop structure lacking a 5'cap and 3'tail. circRNA is stable, difficult to cleave and resistant to RNA exonuclease or RNase R degradation. circRNA molecules have several clinical applications, especially in tumors. For instance, circRNA may be used for non‑invasive diagnosis, therapy and prognosis. Exosomes play a crucial role in the development of tumors. Exosomal circRNA in particular has led to increased research interest into tumorigenesis and tumor progression. Additionally, exosomal circRNA plays a role in cell‑cell communication. Exosomal circRNA facilitates tumor metastasis by altering the tumor microenvironment and the pre‑metastatic niche. Additionally, studies have revealed the mechanism by which exosomal circRNA affects malignant progression through signal transduction. Moreover, exosomal circRNA promotes tumor metastasis by regulating gene expression, RNA transcription and protein translation. In this review, the biological features and clinical application of exosomal circRNA are described, highlighting the underlying mechanisms through which they regulate tumor metastasis. The application of circRNA as clinical diagnostic biomarkers and in the development of novel therapeutic strategies is also discussed.Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non‑Hodgkin lymphoma that is unique and different from systemic diffuse large B‑cell lymphomas. The median age at diagnosis of PCNSL is 65 years and its incidence is rising rapidly in the elderly population. A total of ≥20% of all patients with PCNSL are ≥80 years old. Notably, age has been identified as an independent poor prognostic factor for PCNSL. Elderly patients have an inferior prognosis to that of younger patients and are more severely affected by iatrogenic toxicity; therefore, elderly patients represent a unique and vulnerable treatment subgroup. The present review summarized the available literature to provide an improved understanding of the epidemiology, clinical characteristics, diagnosis, prognosis and management of PCNSL in the elderly population. Notably, the incidence of PCNSL in immunocompetent elderly patients, predominantly in men, is increasing. For the diagnosis of CNSL, imaging‑guided stereotactic biopsy is considered the gold standard. When stereotactic biopsy is not possible or conclusive, certain biomarkers have been described that can help establish a diagnosis. PCNSL has a very poor prognosis in the elderly, even though several prognostic scoring systems exist and several prognostic markers have been reported in patients with PCNSL. Furthermore, the treatment of elderly patients remains challenging; it is unlikely that a novel agent could be used as a curative monotherapy; however, a combination of novel agents with polychemotherapy or its combination with other novel drugs may have therapeutic potential.The aim of the present study was to explore the mechanism by which microRNA (miR)‑642a‑5p regulates the migration and invasion of colon cancer cells via collagen type I α1 (COL1A1). The characteristics of miR‑642a‑5p and COL1A1 were analysed through bioinformatics. Cancer and normal tissues were collected from patients with colon cancer. miR‑642a‑5p‑ and COL1A1‑overexpressing cell lines were constructed by transfection. A dual‑luciferase reporter assay was used to verify the targeting of COL1A1 by miR‑642a‑5p. Cell Counting Kit‑8, wound healing and Transwell assays were used to detect cell viability, migration and invasion, respectively. link2 Protein and mRNA expression levels were examined by western blotting and reverse transcription‑quantitative PCR, respectively. The results revealed that miR‑642a‑5p expression was significantly upregulated and COL1A1 expression was downregulated in patients with colon cancer. Low levels of miR‑642a‑5p and high levels of COL1A1 were associated with a poor prognosis in patients with colon cancer. miR‑642a‑5p directly targeted the 3'‑untranslated region of COL1A1 and inhibited COL1A1 expression. Overexpression of miR‑642a‑5p inhibited cell viability, migration, invasion and epithelial mesenchymal transition. Overexpression of COL1A1 promoted cell viability, migration, invasion and EMT, and partially reversed the inhibitory effects of miR‑642a‑5p on colon cancer cells. In conclusion, miR‑642a‑5p inhibited colon cancer cell migration, invasion and EMT by regulating COL1A1.Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide, with an unsatisfactory prognosis, although treatments are improving. One of the main challenges for the treatment of HCC is the prevention or management of recurrence and metastasis of HCC. It has been found that chemokines and their receptors serve a pivotal role in HCC progression. In the present review, the literature on the multifactorial roles of exosomes in HCC from PubMed, Cochrane library and Embase were obtained, with a specific focus on the functions and mechanisms of chemokines in HCC. To date, >50 chemokines have been found, which can be divided into four families CXC, CX3C, CC and XC, according to the different positions of the conserved N‑terminal cysteine residues. Chemokines are involved in the inflammatory response, tumor immune response, proliferation, invasion and metastasis via modulation of various signaling pathways. Thus, chemokines and their receptors directly or indirectly shape the tumor cell microenvironment, and regulate the biological behavior of the tumor. In addition, the potential application of chemokines in chemotaxis of exosomes as drug vehicles is discussed. Exosomes containing chemokines or expressing receptors for chemokines may improve chemotaxis to HCC and may thus be exploited for targeted drug delivery.Leukemia stem cells (LSCs), which evade standard chemotherapy, may lead to chemoresistance and disease relapse. The overexpression of ATP‑binding cassette subfamily G member 2 (ABCG2) is an important determinant of drug resistance in LSCs and it can serve as a marker for LSCs. Targeting ABCG2 is a potential strategy to selectively treat and eradicate LSCs, and, hence, improve leukemia therapy. Tucatinib (Irbinitinib) is a novel tyrosine kinase inhibitor, targeting ErbB family member HER2, and was approved by the Food and Drug Administration in April 2020, and in Switzerland in May 2020 for the treatment of HER2‑positive breast cancer. In the present study, the results demonstrated that tucatinib significantly improved the efficacy of conventional chemotherapeutic agents in ABCG2‑overexpressing leukemia cells and primary leukemia blast cells, derived from patients with leukemia. link3 In addition, tucatinib markedly decreased the proportion of leukemia stem cell‑like side population (SP) cells. In SP cells, isolated from leukemia cells, the intracellular accumulation of Hoechst 33342, which is an ABCG2 substrate, was significantly elevated by tucatinib. Furthermore, tucatinib notably inhibited the efflux of [3H]‑mitoxantrone and, hence, there was a higher level of [3H]‑mitoxantrone in the HL60/ABCG2 cell line. The result from the ATPase assay revealed that tucatinib may interact with the drug substrate‑binding site and stimulated ATPase activity of ABCG2. However, the protein expression level and cellular location of ABCG2 were not affected by tucatinib treatment. Taken together, these data suggested that tucatinib could sensitize conventional chemotherapeutic agents, in ABCG2‑overexpressing leukemia cells and LSCs, by blocking the pump function of the ABCG2 protein. The present study revealed that combined treatment with tucatinib and conventional cytotoxic agents could be a potential therapeutic strategy in ABCG2‑positive leukemia.Maltose, the major product of starch breakdown in Arabidopsis (Arabidopsis thaliana) leaves, exits the chloroplast via the maltose transporter MEX1. Consequently, mex1 loss-of-function plants exhibit substantial maltose accumulation, a starch-excess phenotype and a specific chlorotic phenotype during leaf development. Here, we investigated whether the introduction of an alternative metabolic route could suppress the marked developmental defects typical for mex1 loss-of-function mutants. To this end, we ectopically expressed in mex1 chloroplasts a functional maltase from bakeŕs yeast (Saccharomcyes cerevisiae, cpMAL mutants). Remarkably, the stromal maltase activity substantially alleviates most phenotypic peculiarities typical for mex1 plants. However, the cpMAL lines contained only slightly less maltose than parental mex1 plants and their starch levels were, surprisingly, even higher. These findings point to a threshold level of maltose responsible for the marked developmental defects in mex1. While growth and flowering time were only slightly retarded, cpMAL lines exhibited a substantially improved frost tolerance, when compared to wild types. In summary, these results demonstrate the possibility to bypass the MEX1 transporter, allow us to differentiate between possible starch-excess and maltose-excess responses, and demonstrate that stromal maltose accumulation prevents frost defects. The latter insight may be instrumental for the development of crop plants with improved frost tolerance.In cyanobacteria, the PII protein (the glnB gene product) regulates a number of proteins involved in nitrogen assimilation including PipX, the co-activator of the global nitrogen regulator protein NtcA. In Synechococcus elongatus PCC 7942, construction of a PII-less mutant retaining the wild-type pipX gene is difficult because of the toxicity of uncontrolled action of PipX and the other defect(s) resulting from the loss of PII per se, but the nature of the PipX toxicity and the PipX-independent defect(s) remains unclear. Characterization of a PipX-less glnB mutant (PD4) in this study showed that the loss of PII increases the sensitivity of PSII to ammonium. Ammonium was shown to stimulate formation of reactive oxygen species in the mutant cells. The ammonium-sensitive growth phenotype of PD4 was rescued by addition of an antioxidant α-tocopherol, confirming that photo-oxidative damage was the major cause of the growth defect. A targeted PII mutant retaining wild-type pipX was successfully constructed from the wild-type S.