第9卷，第6期

There are over 170 types of chemical modifications discovered across all the RNA categories in living organisms, which constitute the epitranscriptome. Emerging as an additional mechanism of post-transcriptional regulation of genetic information, these RNA modifications and the epitranscriptome have been tightly associated with the RNA fate and various human diseases. Among these distinct RNA modifications, m⁶A is the most prevalent and involved in coordinating many aspects of biological activities. It has been known that the deposition and removal of the m⁶A modification are dynamic and reversible processes in cells and regulated by different groups of enzymes and proteins, including the m⁶A writers, erasers and readers. The m⁶A writers include the methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14) and Wilms’ tumor 1-associating protein (WTAP), which are responsible for adding the methyl group to N6 position on adenosine to generate the m⁶A modification, and the fat-mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5) have been identified as the enzymes to remove it. The YTH family and heterogenous nuclear ribonucleoproteins (HNRNPs) as well as the eukaryotic initiation factor (eIF) and insulin like growth factor 2 (IGF2) are discovered to be the endogenous proteins to recognize the m⁶A modification and mediate its biological functions. Dissecting the precise roles of m⁶A in biological or disease processes has been complicated by the fact that the m⁶A's function is position, transcript, cell and tissue contextdependent. Conventional genetic methods manipulating m⁶A writers and erasers not only lead to the global change of m⁶A levels across the whole transcriptome but also lack temporal controls. Without proper research tools, the relationship between m⁶A and the phenotypic outcomes within particular RNA and cellular contexts remains elusive.

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Phosphatidylinositol 3-kinases (PI3Ks) play key roles in tumorigenesis. PIK3CA, which encodes PI3K complex catalytic subunit p110α, is one of the most frequently mutated oncogenes in human cancers. So, targeting p110α holds great promise for cancer therapy. Alpelisib, a small molecule inhibitor specifically targeting PIK3CA/p110α, has been approved by FDA to treat HR-positive and HER2-negative breast cancer patients harboring PIK3CA gene mutations. Most PIK3CA/p110α mutations occur at two hot spot regions: an acidic cluster (E542, E545, and Q546) in the helical domain and a histidine residue (H1047) in the kinase domain. Although all these hot-spot mutations activate the PI3-kinase activity, p110α helical domain mutations and kinase domain mutations promote tumorigenesis through different molecular mechanisms. Moreover, PIK3CA helical domain mutant tumors were less responsive to alpelisib treatment compared with PIK3CA H1047R mutant tumors in early clinical trials, while the mechanism has not been clearly clarified. Therefore, it is important to investigate the oncogenic mechanism and develop a more effective therapeutic strategy for tumors with PIK3CA helical domain mutations.

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Rett syndrome (RTT) is a rare X-linked brain disorder predominantly in females, caused by mutations in Methyl-CpG-Binding Protein2 (MECP2) gene with the characteristic features of progressive developmental delay, severe intellectual disability, microcephaly, retarded growth, loss of communication abilities, loss of purposeful hand movements, abnormal walking or gait abnormalities, repetitive hand movements, abnormal breathing, irritability and abnormal behaviours. Over the last five years, more than eighty genes related to RTT were found using next generation sequencing. Here we presented a comprehensive clinical report of a 38-year-old RTT woman having de novo heterozygous Laminin Subunit Gamma 3 gene (LAMC3) mutation G>A (Chr9:133944387; p.C947Y) links with RTT neurological dysfunctions, brain malformations, reduced brain volume and hypoplasia of corpus callosum. This new finding supports the possibility of targeting LAMC3 gene for rescuing the neuropathology of RTT. Other deleterious mutations found in genes such as, CACNA1B (rs4422842), CUBN (rs2271460), GPATCH3 (rs779537923), TUBB1 (rs463312), KCNJ5 (rs768906222), VWA5A (rs551469534), DNAAF1 (rs751148678), and PARP1 (rs3219145) were unreported in RTT patients.

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Lipid droplets (LDs) are lipid storage organelles with a central hydrophobic core of neutral lipids that is enclosed in a monolayer of phospholipids. Though the storage of lipids, mainly cholesterol and triglycerides, was thought to be the primary function of LDs, studies have shown that they have important functions in maintaining lipid homeostasis and modulating various signaling pathways. Abnormal lipid accumulation has been recognized as a key feature in several human diseases such as obesity, diabetes, cancer, neurological diseases, cardiovascular diseases, insulin resistance, liver diseases and kidney diseases. LDs play an important role in innate immunity, in the fight against infections, and in the replication of SARS-CoV-2. Hence a tight regulation of LD metabolism is essential for proper functioning of a cell. We previously reported an important role for LD accumulation and the progression of kidney diseases, including diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). In FSGS, we found that glomerular LD accumulation coincided with decreased expression of sphingomyelinase phosphodiesterase like 3b (SMPDL3b), an enzyme we showed to regulate ceramide-1-phosphate levels in podocytes, suggesting a role for SMPDL3b in sphingolipid metabolism. However, if SMPDL3b regulates LD homeostasis is unknown. The present study was aimed at determining if SMPDL3b regulates LD homeostasis in immortalized human podocytes, which are terminally differentiated cells that have a key role in the glomerular filtration barrier. We found that SMPDL3b is localized to LDs and that reduced expression of SMPDL3b is associated with an increase in the number of LDs, increased levels of triglycerides (TAG) and cholesterol esters, increased uptake of fatty acids and decreased lipolysis. Reduced expression of SMPDL3b leads to an increase in PLIN5, heat shock cognate protein (HSC70) and lysosomeassociated membrane protein 2A (LAMP2A) expression. Selonsertib treatment corrected all the phenotypes observed in immortalized human podocytes with reduced SMPDL3b expression.

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Autophagy, a conserved “self-eating” process for cellular homeostasis, plays a crucial role in the hepatitis B virus (HBV) life cycle, including viral assembly, envelopment, release, and degradation. Autophagy can also be hijacked by HBV for its persistence and survival. However, the association between HBV mutations and autophagy remains unclear. Herein, we found that an HBV surface antigen (HBsAg) mutation involving sL13H substitution impaired HBsAg expression and caused its abnormal distribution in vitro and in a hydrodynamic injection (HI)-based mouse model for acute HBV infection. The sL13H mutation also decreased autophagosome formation and inhibited autophagic flux. Further mechanistic analysis revealed that sL13H suppresses HBV-induced autophagy initiation by inhibiting the eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3/PERK)-eukaryotic translation initiation factor 2 subunit alpha (EIF2S1/eIF2α)-autophagy related (ATG)5/12 axis. Therefore, our findings reveal a potential role for HBV mutations in manipulating host autophagic flux for virus persistence and pathogenesis in chronic hepatitis B.

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Human genome encodes six paralogous gasdermin genes: GSDMA, GSDMB, GSDMC, GSDMD, GSDME and DFNB59. Proteolytic cleavage of these gasdermin proteins liberates an N-terminal (NT) fragment from autoinhibition, which assembles in membrane to form pores and execute pyroptotic cell death in general. In contrast to other gasdermins, gasdermin B (GSDMB) is the only gasdermin gene that has not been identified in rodents. Zhou et al first shed light on the molecular mechanism by which cytotoxic lymphocyte- derived granzyme A (GZMA) cleaves GSDMB to execute pyroptosis in GSDMB-positive cells, especially in cancer cells. In this issue of Cell, Hansen et al reported a dynamic host pathogen S. flexneri prevents GSDMB-mediated lysis by secreting IpaH7.8, which targets and ubiquitinates GSDMB for 26S proteasome destruction. They showed that GSDMB implements bacteriocidic ability by recognition of the phospholipids on Gram-negative bacterial membranes rather than lysing host cells. Although their experimental design and data are clearly presented and straightforward, there are still some doubts to be clarified.

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Reprogramming of metabolic pathways, a hallmark of human cancer, results from a process in which cancer cells become dependent on specific metabolic pathways such as glutamine catabolism or glutaminolysis for growth and survival. Previous studies have demonstrated that triplenegative breast cancers (TNBC) may use glutamine as an extracellular nutrient source to generate lipids, proteins, and nucleic acids. Glutamine catabolism in cancer cells also contributes to the production of the antioxidant, glutathione (GSH), which is critical for redox homeostasis and for protection of cells from oxidative stress elicited by reactive oxygen species (ROS). Considering TNBC cell lines are often dependent on glutamine for growth and survival, we sought to determine whether targeting glutaminolysis with a small molecule inhibitor, CB-839, in combination with platinum-based chemotherapy drug, would elicit significant anti-tumor activity.

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Resistance to chemotherapy is a prominent clinical problem in high grade serous ovarian cancer (HGSOC). An inadequate understanding of adaptive signaling coupled with limited treatment options for a chemoresistant tumor are likely causes for poor outcomes. We previously reported that BMI1, a stem-cell factor is instrumental in regulating chemoresistance. However, to advance anti-BMI1 therapy from the bench to the bedside, efficacy needs to be tested in patient-derived chemoresistant HGSOC models, which is lacking. Here, we report generation and characterization of a chemoresistant, patient-derived xenograft (PDX) model of HGSOC that recapitulates carboplatin and paclitaxel resistance observed in the patient. We demonstrate that the combination of standard therapy (carboplatin and paclitaxel) along with PTC596 also known as Unesbulin, a clinical inhibitor of BMI1 mitigates chemoresistance and significantly decreases the tumor growth compared to either therapy alone. Mechanistically, PTC596 treatment decreases expression of cancer stem-like markers in tumor tissues, along with a decrease in proliferative and an increase in apoptotic markers, thereby overcoming chemoresistance. Thus, patients with chemoresistant cancer that have limited treatment options may benefit from combination of anti-BMI1 strategies with standard chemotherapy.

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Constricted oxygen and glucose supplies are common conditions that healthy cells following a stress such an ischemic insult as well as cancer cells within a solid tumor need to overcome in order to survive. These conditions are a serious challenge for cells, which accurately measure the impact to make a life or death decision. In cancer cells, aberrant gene expression and/or protein regulation, frequently linked to appearing mutations, may confer selective advantages to survive under these adverse conditions. In the past years, cumulative evidence indicates that protein modification by covalent attachment of the Small Ubiquitin-like MOdifier (SUMO) plays a role in cell survival after oxygen and glucose deprivation (OGD). Sumoylation involves maturation of SUMO, E1 (SAE1/UBA2)-mediated activation and transfer to the E2 conjugating enzyme (UBC9), to be attached to target proteins, which is frequently facilitated by a E3 ligase, with PIAS as the most investigated proteins. Specific SUMO proteases such as the SENP family members are involved in maturation and recycling SUMO from targets. SUMO is essential in vertebrates, participates in most physiological processes and is associated with cancer. Three functional SUMO molecules have been identified in humans: SUMO1, 2 and 3. SUMO2 and 3, usually referred to as SUMO2/3, are highly homologous and undistinguishable, and are abundant in the cell as unconjugated to rapidly modify proteins in response to OGD. From the initial observation of increased SUMO2/3 conjugation in squirrel brain during hibernation torpor a number of reports have described protection effects of sumoylation in ischemic/reperfusion models, and established better outcomes in cell viability associated with SUMO or UBC9 overexpression and worse outcomes associated with SUMO silencing or SENP1 overexpression. However, sumoylation of heterochromatin protein 1 α (HP1α) has been linked to senescence in cancer cells. To define molecular relevant aspects of SUMO-mediated response to OGD, we have investigated gene expression regulation of the sumoylation pathway components. Notably we found that Senp7 gene and protein are downregulated in OGD-treated cancer cells. Interestingly, SENP7 overexpression under these conditions increased cell survival, while downregulation potentiated OGD-triggered apoptosis. In contrast, SENP3 promoted cell death. These observations are in agreement with prevalent amplification of SENP7 and deletion of SENP3 genomic regions in many cancer types. More importantly, in colon cancer, high expression of SENP7 correlated with both, poor prognosis and higher transformation degree.

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Heterozygous single nucleotide variants (SNVs) or copynumber variant (CNV) deletions, involving the mesenchymal forkhead box family transcription factor gene, FOXF1, or its distant lung-specific enhancer, are responsible for 80%-90% of cases of alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). ACDMPV is a lethal lung developmental disorder with severe progressive respiratory failure and persistent pulmonary arterial hypertension (Supplemental Material). Intriguingly, in contrast to point mutations in FOXF1, the ACDMPV-causative CNV deletions arise de novo almost exclusively on the maternal chromosome 16q24.1. Thus far, we and others have described 50 de novo CNV deletions that arose on maternal chromosome 16 and only three de novo CNV deletions that arose on paternal chromosome 16q24.1. Here, we define an~660 bp ultra-conserved non-coding interval (660UCR) within the FOXF1 enhancer as critical for FOXF1 cis-regulation and normal human lung development. Heterozygous loss of this region on paternal chromosome 16 was found causative for ACDMPV. We also describe a novel enhancer lncRNA gene, RP11-805I24.3, located in the proximity to 660UCR and overlapping another ~1 kb ultra-conserved interval (1000UCR), as essential for the FOXF1 expression. Based on the obtained data, we propose a bimodal structure and parental functional dimorphism of the FOXF1 enhancer.

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Pancreatic cancer, mostly pancreatic ductal adenocarcinoma (PDAC), is often metastatic upon the initial diagnosis, and has a high mortality rate. However, the primary and the matched metastatic cancers often share the same driver gene mutations. Gene expression comparison between primary and metastatic PDAC tissues revealed high expression of Gli2 and YAP1 in the metastatic PDAC. Gli2 is an important player in non-canonical hedgehog signaling, and YAP1 is an essential cell polarity gene. In this study, we investigated the effects of Gli2 and YAP1 on pancreatic cancer cell function in 3D culture and in mouse models. We further determined the relationship between Gli2 and YAP1. These studies further our understanding of pancreatic cancer metastasis.

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Transfer RNAs (tRNAs) are essential for protein synthesis. Mature or pre-tRNAs may be cleaved to produce tRNA-derived small RNAs (tsRNAs). tsRNAs, divided into tRNA-derived stress-induced RNA (tiRNAs) and tRNA-derived fragments (tRFs), play versatile roles in a number of fundamental biological processes. tsRNAs not only play regulatory roles in gene silencing, RNA stability, reverse transcription, and translation, but are also closely related to cell proliferation, migration, cell cycle, and apoptosis. Their abnormal expression is associated with the occurrence and development of various human diseases, especially cancer. This paper reviews the classification, biogenesis, and mechanism of action of tsRNAs, and the research progress to date on tsRNAs in cancers. These findings provide new opportunities for diagnostic biomarkers and treatment targets of several types of cancers including gastric cancer, colorectal cancer, hepatocellular carcinomas, pancreatic cancer, breast cancer, prostate cancer, renal cell carcinoma, ovarian cancer, lung cancer, bladder cancer, thyroid cancer, oral cancer, and leukemia.

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Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. OC is usually detected at the advanced stages of the disease, making it highly lethal. miRNAs are single-stranded, small non-coding RNAs with an approximate size ranging around 22 nt. Interestingly, a considerable proportion of miRNAs are organized in clusters with miRNA genes placed adjacent to one another, getting transcribed together to result in miRNA clusters (MCs). MCs comprise two or more miRNAs that follow the same orientation during transcription. Abnormal expression of the miRNA cluster has been identified as one of the key drivers in OC. MC exists both as tumor-suppressive and oncogenic clusters and has a significant role in OC pathogenesis by facilitating cancer cells to acquire various hallmarks. The present review summarizes the regulation and biological function of MCs in OC. The review also highlights the utility of abnormally expressed MCs in the clinical management of OC.

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Acute myeloid leukemia (AML) is a malignant hematological tumor with disordered oncogenes/tumor suppressor genes and limited treatments. The potent anti-cancer effects of bromodomain and extra-terminal domain (BET) inhibitors, targeting the key component of super enhancers, in early clinical trials on AML patients, implies the critical role of super enhancers in AML. Here, we review the concept and characteristic of super enhancer, and then summarize the current researches about super enhancers in AML pathogenesis, diagnosis and classification, followed by illustrate the potential super enhancer-related targets and drugs, and propose the future directions of super enhancers in AML. This information provides integrated insight into the roles of super enhancers in this disease.

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Sexual dimorphism has been reported in various human diseases including autoimmune diseases, neurological diseases, pulmonary arterial hypertension, and some types of cancers, although the underlying mechanisms remain poorly understood. The long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in X chromosome inactivation (XCI) in female placental mammals, a process that ensures the balanced expression dosage of X-linked genes between sexes. XIST is abnormally expressed in many sex-biased diseases. In addition, escape from XIST-mediated XCI and skewed XCI also contribute to sex-biased diseases. Therefore, its expression or modification can be regarded as a biomarker for the diagnosis and prognosis of many sex-biased diseases. Genetic manipulation of XIST expression can inhibit the progression of some of these diseases in animal models, and therefore XIST has been proposed as a potential therapeutic target. In this manuscript, we summarize the current knowledge about the mechanisms for XIST-mediated XCI and the roles of XIST in sex-biased diseases, and discuss potential therapeutic strategies targeting XIST.

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Annexin A1, a well-known endogenous anti-inflammatory mediator, plays a critical role in a variety of pathological processes. Fibrosis is described by a failure of tissue regeneration and contributes to the development of many diseases. Accumulating evidence supports that Annexin A1 participates in the progression of tissue fibrosis. However, the fundamental mechanisms by which Annexin A1 regulates fibrosis remain elusive, and even the functions of Annexin A1 in fibrotic diseases are still paradoxical. This review focuses on the roles of Annexin A1 in the development of fibrosis of lung, liver, heart, and other tissues, with emphasis on the therapy potential of Annexin A1 in fibrosis, and presents future research interests and directions in fibrotic diseases.

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Anoctamin-5 (ANO5) is a multi-pass membrane protein localized to the sarcolemma and the sarcoplasmic reticulum. Mutations were linked to rare autosomal recessive muscle diseases. Here, we summarize the clinical spectrum, imaging data and molecular research findings as well as results of animal modeling, which significantly moved forward the understanding of mechanisms underlying ANO5-related muscle diseases. Given that precise histological information on inflammatory processes taking place in patient-derived muscle are still lacking, an (immuno)histological study on biopsies derived from six ANO5-patients was performed showing focal accumulation of necrotic fibers, mild fiber-size variances and myophagocytosis. In addition, MRI data of four ANO5-patients (including a 10-year follow-up in one patient) are presented and discussed in the context of previously published MRI- findings. Hence, data presented in this article combining a review of the literature with own myopathological findings address scientific trends and open questions on ANO5-related muscle diseases, which would be of significant interest for a wide neuromuscular diseases community. To conclude, a clear genotyp-ephenotype correlation does not exist, and ANO5-related muscle disorders might represent the next entity of a clinical continuum with varying degree of muscle cell pathologies. In addition, results of pre-clinical studies allowed the definition of suitable cell and animal models characterized by certain histological and functional pathologies resembling the human phenotype. These models might serve as suitable systems for testing of interventional concepts in future.

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Cutaneous melanoma is a common cancer and cases have steadily increased since the mid 70s. For some patients, early diagnosis and surgical removal of melanomas is lifesaving, while other patients typically turn to molecular targeted therapies and immunotherapies as treatment options. Easy sampling of melanomas allows the scientific community to identify the most prevalent mutations that initiate melanoma such as the BRAF, NRAS, and TERT genes, some of which can be therapeutically targeted. Though initially effective, many tumors acquire resistance to the targeted therapies demonstrating the need to investigate compensatory pathways. Immunotherapies represent an alternative to molecular targeted therapies. However, inter-tumoral immune cell populations dictate initial therapeutic response and even tumors that responded to treatment develop resistance in the long term. As the protocol for combination therapies develop, so will our scientific understanding of the many pathways at play in the progression of melanoma. The future direction of the field may be to find a molecule that connects all of the pathways. Meanwhile, noncoding RNAs have been shown to play important roles in melanoma development and progression. Studying noncoding RNAs may help us to understand how resistance - both primary and acquired - develops; ultimately allow us to harness the true potential of current therapies. This review will cover the basic structure of the skin, the mutations and pathways responsible for transforming melanocytes into melanomas, the process by which melanomas metastasize, targeted therapeutics, and the potential that noncoding RNAs have as a prognostic and treatment tool.

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Neuroblastoma (NB), which is the most common pediatric extracranial solid tumor, varies widely in its clinical presentation and outcome. NB has a unique ability to spontaneously differentiate and regress, suggesting a potential direction for therapeutic intervention. However, the underlying mechanisms of regression remain largely unknown, and more reliable prognostic biomarkers are needed for predicting trajectories for NB. We performed scRNAseq analysis on 17 NB clinical samples and three peritumoral adrenal tissues. Primary NB displayed varied cell constitution, even among tumors of the same pathological subtype. Copy number variation patterns suggested that neuroendocrine cells represent the malignant cell type. Based on the differential expression of sets of related marker genes, a subgroup of neuroendocrine cells was identified and projected to differentiate into a subcluster of benign fibroblasts with highly expressed CCL2 and ZFP36, supporting a progressive pathway of spontaneous NB regression. We also identified prognostic markers (STMN2, TUBA1A, PAGE5, and ETV1) by evaluating intra-tumoral heterogeneity. Lastly, we determined that ITGB1 in M2-like macrophages was associated with favorable prognosis and may serve as a potential diagnostic marker and therapeutic target. In conclusion, our findings reveal novel mechanisms underlying regression and potential prognostic markers and therapeutic targets of NB.

1290

Understanding the association between the genetic and clinical phenotypes in children with nephrotic syndrome (NS) of different etiologies is critical for early clinical guidance. We employed whole-exome sequencing (WES) to detect monogenic causes of NS in a multicenter cohort of 637 patients. In this study, a genetic cause was identified in 30.0% of the idiopathic steroid-resistant nephrotic syndrome (SRNS) patients. Other than congenital nephrotic syndrome (CNS), there were no significant differences in the incidence of monogenic diseases based on the age at manifestation. Causative mutations were detected in 39.5% of patients with focal segmental glomerulosclerosis (FSGS) and 9.2% of those with minimal change disease (MCD). In terms of the patterns in patients with different types of steroid resistance, a single gene mutation was identified in 34.8% of patients with primary resistance, 2.9% with secondary resistance, and 71.4% of children with multidrug resistance. Among the various intensified immunosuppressive therapies, tacrolimus (TAC) showed the highest response rate, with 49.7% of idiopathic SRNS patients achieving complete remission. Idiopathic SRNS patients with monogenic disease showed a similar multidrug resistance pattern, and only 31.4% of patients with monogenic disease achieved a partial remission on TAC. During an average 4.1-year follow-up, 21.4% of idiopathic SRNS patients with monogenic disease progressed to end-stage renal disease (ESRD). Collectively, this study provides evidence that genetic testing is necessary for presumed steroid-resistant and idiopathic SRNS patients, especially those with primary and/or multidrug resistance.

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All-trans retinoic acid (ATRA) can reverse the malignant behaviors of hepatocellular carcinoma (HCC) cells, thereby exerting anti-HCC effect; however, the underlying mechanism is yet to be understood. This study aimed to demonstrate that ATRA is vital to ferroptosis in HCC. Ferroptosis-related genes exhibit different expression in patients with HCC compared to that in healthy individuals. A total of 20 amino acid products were detected in HepG2 cells, the expression level of 5 was decreased after ATRA treatment. ATRA improved the levels of lipid ROS, MDA, and NAPD⁺/NADPH, and reduced the mt-DNA copy number and changed the structure of mitochondria, in HepG2 and Hep3B cells. We found the expression of genes positively correlated with ferroptosis to increase and those negatively correlated to decrease with ATRA treatment. Inhibition of ferroptosis by Ferrostatin-1 reversed ATRA-inhibited proliferation of HCC cells, along with cell migration and invasion. GSH synthesis was blocked by ATRA, accompanied by decreased cystine content and increased glutamate content, and downregulation of the expression of GSH synthesis-related genes. Our findings suggested that ATRA inhibited the malignancy of HCC cells by improving ferroptosis, and that inhibition of GSH synthesis contributed to ATRA-induced ferroptosis.

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The authors regret that some statistical errors were made in “Lipopolysaccharide-induced podocyte injury is regulated by calcineurin/NFAT and TLR4/MyD88/NF-κB signaling pathways through Angiopoietin-like protein 4” (Genes Dis, https://doi.org/10.1016/j.gendis.2020.07.005) at Figure 2G, Figure 3B and F, and Figure 4C and D for Angptl4 expression, Figure 5E for CaN expression. For these quantitative results, which should be used with one-way ANOVA statistical methods, but authors wrongly used T-test between two groups during the submission of the original manuscript, and they did not notice these errors during the submission of the original manuscript. Furthermore, the strain of the mice described in the materials and methods should be C57/BL/6 mice. Moreover, in Fig.S3a of the original manuscript, it should be the mRNA expression of CD14, not the mRNA expression of Angptl4. With this change in the figures, the authors confirm that this correction does not alter the conclusions in the manuscript.

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