Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Nov. 1, 2022

Colorectal cancer (CRC) is the third most common and second leading cause of cancer-related death worldwide. Countless CRC patients undergo disease progression. As a hallmark cancer, Warburg effect promotes metastasis remodels tumor microenvironment, including promoting angiogenesis, immune suppression, cancer-associated fibroblasts formation drug resistance. Targeting metabolism would be promising method for treatment CRC. In this review, we summarize information about roles in microenvironment to elucidate mechanisms governing identify novel targets therapy.

Language: Английский

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Hypoxic Tumor-Derived Exosomal Long Noncoding RNA UCA1 Promotes Angiogenesis via miR-96-5p/AMOTL2 in Pancreatic Cancer

Molecular Therapy — Nucleic Acids, Journal Year: 2020, Volume and Issue: 22, P. 179 - 195

Published: Aug. 25, 2020

The hypoxic microenvironment, an important feature of solid tumors, promotes tumor cells to release exosomes and enhances angiogenesis. However, the detailed functions mechanisms underlying their effects in pancreatic cancer (PC) remain mysterious. Here, we observed that derived from PC promoted cell migration tube formation human umbilical vein endothelial (HUVECs). long noncoding RNA (lncRNA) UCA1, a key factor, was highly expressed could be transferred HUVECs through exosomes. In addition, expression levels UCA1 patients' serum were higher than healthy controls associated with poor survival patients. Moreover, exosomal promote angiogenesis growth both vitro vivo. With respect functional mechanism, acted as sponge microRNA (miR)-96-5p, relieving repressive miR-96-5p on its target gene AMOTL2. Collectively, these results indicate miR-96-5p/AMOTL2/ERK1/2 axis therefore, serve novel for treatment.

Language: Английский

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Hypoxia-induced HIF-1α/lncRNA-PMAN inhibits ferroptosis by promoting the cytoplasmic translocation of ELAVL1 in peritoneal dissemination from gastric cancer

Redox Biology, Journal Year: 2022, Volume and Issue: 52, P. 102312 - 102312

Published: April 9, 2022

Peritoneal metastasis (PM) is the main site of gastric cancer (GC) distant and indicates an extremely poor prognosis survival. Hypoxia a common feature peritoneal metastases up-regulation hypoxia inducible factor 1 alpha (HIF-1α) may be potential driver in occurrence PM. Ferroptosis recently discovered form regulated cell death closely related to development tumors. However, underlying mechanism link HIF-1α ferroptosis PM GC remains unknown. Here, lncRNA-microarrays RNA library construction/lncRNA-seq results shown that lncRNA-PMAN was highly expressed significantly modulated by HIF-1α. Upregulation PMAN associated with patients GC. up-regulated improved stability SLC7A11 mRNA promoting cytoplasmic distribution ELAVL1, which identified RNA-pulldown/mass spectrometry results. Accumulation increases level l-Glutathione (GSH) inhibits accumulation reactive oxygen species (ROS) irons cells. Finally protect cells against induced Erastin RSL3. Our findings have elucidated effect HIF-1α/PMAN/ELAVL1 provides theoretical support for diagnostic biomarkers therapeutic targets

Language: Английский

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Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(20), P. 11047 - 11047

Published: Oct. 13, 2021

Until recently, radiation effects have been considered to be mainly due nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures ionizing (IR) highly depend on activation regulation through other components organelles determine cell survival proliferation capacities. As typical epigenetic-regulated central power stations cells, mitochondria play an important pivotal role in those responses. They direct cellular metabolism, energy supply homeostasis as well radiation-induced signaling, death, immunological This review is focused how energy, dose quality IR affect mitochondria-dependent epigenetic functional control at tissue level. Low-dose appear associated with non-targeted involved genomic instability adaptive responses, whereas high-dose (>1 Gy) concern therapeutic long-term involving mitochondria-mediated innate immune Both quality. For example, increased efficacy high linear transfer particle radiotherapy, e.g., C-ion relies reduction anastasis, enhanced apoptosis immunogenic (antitumor)

Language: Английский

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Exosomes in the hypoxic TME: from release, uptake and biofunctions to clinical applications

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 17, 2022

Abstract Hypoxia is a remarkable trait of the tumor microenvironment (TME). When facing selective pressure, cells show various adaptive characteristics, such as changes in expression cancer hallmarks (increased proliferation, suppressed apoptosis, immune evasion, and so on) more frequent cell communication. Because adaptation to hypoxia, exploring association between communication mediators hypoxia has become increasingly important. Exosomes are important information carriers cell-to-cell Abundant evidence proven that effects TME mediated by exosomes, with occasional formation feedback loops. In this review, we equally focus on biogenesis heterogeneity cancer-derived exosomes their functions under describe known potential mechanism ascribed hypoxia. Notably, call attention size change hypoxic cell-derived characteristic long neglected, propose some possible change. Finally, jointly considering recent developments understanding tumors, noteworthy problems field urgently need be solved for better research clinical application.

Language: Английский

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