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N 6 -Methyladenosine (m 6 A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m 6 A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m 6 A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m 6 A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m 6 A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expression by reducing m 6 A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment. [ABSTRACT FROM AUTHOR]

Background and Objective: About 1% of patients who receive blood transfusions will develop transfusion reactions. Febrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reaction. It not only leads to misdiagnosis and delayed treatment, but also incurs a huge economic burden. This article reviews FNHTR systematically, aiming to make clinicians have a more comprehensive understanding of FNHTR and reduce the occurrence of this side effect., Methods: A comprehensive search of the PubMed, Embase, and Cochrane Library databases was performed. Medical Subject Headings (MeSH) included Blood Transfusion, Transfusion Reaction, and Febrile Non-Hemolytic Transfusion Reaction. The searches and literature screening were performed by 2 researchers; any differences of opinion or results were resolved through negotiation., Key Content and Findings: The pathophysiological mechanisms of FNHTR mainly included immune and non-immune pathways. The former was associated with antibodies against human leukocyte antigen (HLA) produced in transfused patients, while the latter was associated with cytokines released from blood products during storage. Women with a reproductive history and those patients with multiple blood transfusions were more likely to experience FNHTR. Primary hematologic disease, malignant disease, and transfusion with over 6 units of leukocyte-depleted packed red blood cells were independent risk factors for the development of FNHTR. FNHTR could be diagnosed by accompaniment of the fever symptom (body temperature ≥38 ℃, maybe an increase of body temperature of more than 1 ℃ compared with that before blood transfusion) during or within 4 hours after transfusion, or the presence of chills, shakes, headache, and nausea, among other symptoms. FNHTR should be mainly differentiated from other types of transfusion reactions with similar symptoms. Prophylactic strategies for the routine use of antipyretic drugs before transfusion remain controversial. Removal of leukocyte components from blood could reduce the incidence of FNHTR significantly., Conclusions: The pathogenesis of FNHTR is mainly associated with anti-HLA antibodies and cytokines released from blood products during storage. Specific markers and effective detection methods for FNHTR are still lacking. Treatment for FNHTR is currently limited to antipyretic drugs, sedation, and other symptomatic treatment measures. More studies are warranted to focus on the pathological mechanism of FNHTR., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4932/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)