Proto-oncogene FAM83A contributes to casein kinase 1-mediated mitochondrial maintenance and white adipocyte differentiation.

Family with sequence similarity 83 A (FAM83A) is a newly discovered proto-oncogene that has been shown to play key roles in various cancers. However, the function of FAM83A in other physiological processes is not well known. Here, we report a novel function of FAM83A in adipocyte differentiation. We used an adipocyte-targeting fusion oligopeptide (FITC-ATS-9R) to deliver a FAM83A-sgRNA/Cas9 plasmid to knockdown Fam83a (ATS/sg-FAM83A) in white adipose tissue in mice, which resulted in reduced white adipose tissue mass, smaller adipocytes, and mitochondrial damage that was aggravated by a high-fat diet. In cultured 3T3-L1 adipocytes, we found loss or knockdown of Fam83a significantly repressed lipid droplet formation and downregulated the expression of lipogenic genes and proteins. Furthermore, inhibition of Fam83a decreased mitochondrial ATP production through blockage of the electron transport chain, associated with enhanced apoptosis. Mechanistically, we demonstrate FAM83A interacts with casein kinase 1 (CK1) and promotes the permeability of the mitochondrial outer membrane. Furthermore, loss of Fam83a in adipocytes hampered the formation of the TOM40 complex and impeded CK1-driven lipogenesis. Taken together, these results establish FAM83A as a critical regulator of mitochondria maintenance during adipogenesis.

Oroxylin A regulates cGAS DNA hypermethylation induced by methionine metabolism to promote HSC senescence.

Relevant studies have recognized the important role of hepatic stellate cell (HSC) senescence in anti-liver fibrosis. Cellular senescence is believed to be regulated by the cGAS-STING signaling pathway. However, underlying exact mechanisms of cGAS-STING pathway in hepatic stellate cell senescence are still unclear. Here, we found that Oroxylin A could promote senescence in HSC by activating the cGAS-STING pathway. Moreover, activation of the cGAS-STING pathway was dependent on DNMT3A downregulation, which suppressed cGAS gene DNA methylation. Interestingly, the attenuation of DNMT activity relied on the reduction of methyl donor SAM level. Noteworthy, the downregulation of SAM levels implied the imbalance of methionine cycle metabolism, and MAT2A was considered to be an important regulatory enzyme in metabolic processes. In vivo experiments also indicated that Oroxylin A induced senescence of HSCs in mice with liver fibrosis, and DNMT3A overexpression partly offset this effect. In conclusion, we discovered that Oroxylin A prevented the methylation of the cGAS gene by preventing the production of methionine metabolites, which promoted the senescence of HSCs. This finding offers a fresh hypothesis for further research into the anti-liver fibrosis mechanism of natural medicines.

COVID-19-associated liver injury: Adding fuel to the flame.

COVID-19 is mainly characterized by respiratory disorders and progresses to multiple organ involvement in severe cases. With expansion of COVID-19 and SARS-CoV-2 research, correlative liver injury has been revealed. It is speculated that COVID-19 patients exhibited abnormal liver function, as previously observed in the SARS and MERS pandemics. Furthermore, patients with underlying diseases such as chronic liver disease are more susceptible to SARS-CoV-2 and indicate a poor prognosis accompanied by respiratory symptoms, systemic inflammation, or metabolic diseases. Therefore, COVID-19 has the potential to impair liver function, while individuals with preexisting liver disease suffer from much worse infected conditions. COVID-19 related liver injury may be owing to direct cytopathic effect, immune dysfunction, gut-liver axis interaction, and inappropriate medication use. However, discussions on these issues are infancy. Expanding research have revealed that angiotensin converting enzyme 2 (ACE2) expression mediated the combination of virus and target cells, iron metabolism participated in the virus life cycle and the fate of target cells, and amino acid metabolism regulated immune response in the host cells, which are all closely related to liver health. Further exploration holds great significance in elucidating the pathogenesis, facilitating drug development, and advancing clinical treatment of COVID-19-related liver injury. This article provides a review of the clinical and laboratory hepatic characteristics in COVID-19 patients, describes the etiology and impact of liver injury, and discusses potential pathophysiological mechanisms.

Longitudinal links between expressive flexibility and friendship quality in adolescence: The moderating effect of social anxiety.

INTRODUCTION: Expressive flexibility, or the ability to both up- and down-regulate emotional expressions in social interactions, is thought as an indicator and a consequence of healthy interpersonal relationships. The present longitudinal study examined bidirectional associations between expressive flexibility and friendship quality in early adolescence. Since prior research found inconsistent results regarding the adaptiveness of expressive flexibility, which indicated the necessity to consider individual variability in the process, we further tested the potential moderating effect of social anxiety in the links from expressive flexibility to friendship quality. METHODS: Participants from two junior high schools in eastern China (N = 274; 50.4% female; Mage = 13.56) were surveyed at three time points with 6-month intervals. Expressive flexibility, friendship quality, and social anxiety were all assessed via self-reported scales. RESULTS: According to the cross-lagged model results, friendship quality significantly predicted increased expressive flexibility over time. Conversely, the longitudinal association from expressive flexibility to friendship quality was not significant, but the interaction between expressive flexibility and social anxiety significantly predicted later friendship quality. Further analyses via the Johnson-Neyman technique revealed that expressive flexibility only positively predicted friendship quality for adolescents with lower levels of social anxiety. CONCLUSION: Our results suggest that expressive flexibility is not always socially adaptive, so practical interventions that aim to improve youths' social adjustment via expressive flexibility training might need to consider the role of individual characteristics.

Perceptions of Parental Privacy Invasion and Information Management among Chinese Adolescents: Comparing Between- and Within-Family Associations.

The traditional Chinese conceptualization of family privacy is interdependent and hierarchically structured, but mounting evidence suggests that contemporary Chinese youth hold strong desires for individual privacy and respond defensively to perceived parental privacy invasions. The current research examined within-person associations among adolescents' perceptions of parental privacy invasion, secrecy, and disclosure to parents in the Chinese context. This study collected data from 289 Chinese youth (MageT1 = 13.57, SD = 0.63, 50.30% male) at six-month intervals over one year. Random intercept cross-lagged panel modeling (RI-CLPM) showed that stronger perceptions of parental invasion predicted later within-person decreases in adolescents' disclosure and increases in secrecy. Disclosure and secrecy did not predict later perceptions of parental invasion at the within-person level. The findings suggest that Chinese youth manage privacy reactively and defensively when feelings of invasion occur, by decreasing disclosure and increasing secrecy. Stereotypes portraying Chinese youth as highly deferential to parents' demands for informational access might not be representative of adolescents in contemporary society.

Lnc-ORA interacts with microRNA-532-3p and IGF2BP2 to inhibit skeletal muscle myogenesis.

Skeletal muscle is one of the most important organs of the animal body. Long noncoding RNAs play a crucial role in the regulation of skeletal muscle development via several mechanisms. We recently identified obesity-related lncRNA (lnc-ORA) in a search for long noncoding RNAs that influence adipogenesis, finding it impacted adipocyte differentiation by regulating the PI3K/protein kinase B/mammalian target of rapamycin pathway. However, whether lnc-ORA has additional roles, specifically in skeletal muscle myogenesis, is not known. Here, we found that lnc-ORA was significantly differentially expressed with age in mouse skeletal muscle tissue and predominantly located in the cytoplasm. Overexpression of lnc-ORA promoted C2C12 myoblast proliferation and inhibited myoblast differentiation. In contrast, lnc-ORA knockdown repressed myoblast proliferation and facilitated myoblast differentiation. Interestingly, silencing of lnc-ORA rescued dexamethasone-induced muscle atrophy in vitro. Furthermore, adeno-associated virus 9-mediated overexpression of lnc-ORA decreased muscle mass and the cross-sectional area of muscle fiber by upregulating the levels of muscle atrophy-related genes and downregulating the levels of myogenic differentiation-related genes in vivo. Mechanistically, lnc-ORA inhibited skeletal muscle myogenesis by acting as a sponge of miR-532-3p, which targets the phosphatase and tensin homolog gene; the resultant changes in phosphatase and tensin homolog suppressed the PI3K/protein kinase B signaling pathway. In addition, lnc-ORA interacted with insulin-like growth factor 2 mRNA-binding protein 2 and reduced the stability of myogenesis genes, such as myogenic differentiation 1 and myosin heavy chain. Collectively, these findings indicate that lnc-ORA could be a novel underlying regulator of skeletal muscle development.

Efficient Chiral Nanosenor Based on Tip-Modified Nanochannels.

Enantiomers of various drug molecules have a specific effect on living organisms. Accordingly, developing a sample method for the efficient and rapid recognition of chiral drug enantiomers is of great industrial value and physiological significance. Here, inspired by the structure of ion channels in living organisms, we developed a chiral nanosensor based on an artificial tip-modified nanochannel system that allows efficient selective recognition of chiral drugs. In this system, l-alanine-pillar[5]arenes as selective receptors were introduced on the tip side of conical nanochannels to form an enantioselective "gate". The selective coefficient of our system toward R-propranolol is 4.96, which is higher than the traditional fully modified nanochannels in this work.

miR-145-5p attenuates hypertrophic scar via reducing Smad2/Smad3 expression.

The study was designed to explore the underlying mechanism of micro ribonucleic acids (miR)-145-5p in the process of hypertrophic scar (HS). The difference in the relative content of miR-145-5p between HS and adjacent normal skin collected from 5 patients was detected via RT-PCR. Expressions of Smad2 and Smad3 with or without TGF-ß1 was detected by western blotting. Fibroblasts apoptosis rate was examined by Annexin V/Propidium Iodide double staining. HS fibroblasts (HSFs) were isolated from HS tissues, cultured and then divided into control group, miR-145-5p inhibitor group (transfected with miR-145-5p inhibitor) and miR-145-5p mimic group (transfected with miR-145-5p plasmid) based on different treatment methods. Next, CCK-8 was employed to examine the function of miR-145-5p in HSF proliferation. Luciferase assay was conducted to confirm whether Smad2/3 were direct targets of miR-145-5p, and RT-PCR was done to measure the expression of miR-145-5p, Smad2/Smad3 and fibrosis-related genes of fibroblasts in three groups. Wound injury mice model was established to determine the function of miR-145-5p in regulating scar formation. miR-145-5p was found lowly expressed in HS tissues. Compared with Control group, miR-145-5p mimic decreased the levels of Smad2/3, arrested the activation and proliferation of HSFs and induced HSFs apoptosis. Overexpressing miR-145-5p achieved the contrary results. Smad2/3 was confirmed as the target of miR-145-5p. Moreover, miR-145-5p mimic decreased the recruitment of fibroblasts in vivo and decreased the expression of fibrosis-related genes after wound injury. In conclusion, miR-145-5p arrests the development of fibrogenesis and decreases HS formation by reducing the expression of Smad2/3. miR-145-5p may be an optional novel molecular target for treating HS.

Bidirectional effects between expressive regulatory abilities and peer acceptance among Chinese adolescents.

The current study examined potential bidirectional effects between adolescents' expressive regulation (the ability to enhance and suppress overt emotional behavior in line with situational demands) and peer interactions via two experiments. Experiment 1 tested the hypothesis that adolescents' expressive regulation affects their social acceptance from peers. Participants (N = 147) were randomly divided into three conditions and watched video clips in which a same-sex partner differed in his or her levels of expressive enhancement and suppression abilities. Results showed that participants reported greater liking of the partner when he or she was able to flexibly enhance and suppress emotional expressions in line with situational demands compared with when either one of these abilities was impaired. Experiment 2 then examined whether peer rejection reduced participants' enhancement and suppression abilities. We manipulated participants' feelings of rejection through a virtual Cyberball game. Following this manipulation (N = 100; Inclusion vs. Exclusion), we tested participants' expressive enhancement and suppression abilities, as well as their natural expressivity, via an observational task. Peer exclusion resulted in lower levels of enhancement ability and natural expressive behaviors but did not impair suppression ability. The results of these experiments suggest that both expressive enhancement and expressive suppression are important for adolescents to obtain higher peer acceptance. In addition, peer exclusion also caused impairments in expressive regulation, specifically reduced enhancement abilities. In summary, these results evidenced the bidirectional effects between expressive regulation and peer acceptance.

MicroRNA-664-5p promotes myoblast proliferation and inhibits myoblast differentiation by targeting serum response factor and Wnt1.

MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression at the post-transcriptional level and are involved in the regulation of the formation, maintenance, and function of skeletal muscle. Using miRNA sequencing and bioinformatics analysis, we previously found that the miRNA miR-664-5p is significantly differentially expressed in longissimus dorsi muscles of Rongchang pigs. However, the molecular mechanism by which miR-664-5p regulates myogenesis remains unclear. In this study, using flow cytometry, 5-ethynyl-2'-deoxyuridine staining, and cell count and immunofluorescent assays, we found that cell-transfected miR-664-5p mimics greatly promoted proliferation of C2C12 mouse myoblasts by increasing the proportion of cells in the S- and G2-phases and up-regulating the expression of cell cycle genes. Moreover, miR-664-5p inhibited myoblast differentiation by down-regulating myogenic gene expression. In contrast, miR-664-5p inhibitor repressed myoblast proliferation and promoted myoblast differentiation. Mechanistically, using dual-luciferase reporter gene experiments, we demonstrated that miR-664-5p directly targets the 3'-UTR of serum response factor (SRF) and Wnt1 mRNAs. We also observed that miR-664-5p inhibits both mRNA and protein levels of SRF and Wnt1 during myoblast proliferation and myogenic differentiation, respectively. Furthermore, the activating effect of miR-664-5p on myoblast proliferation was attenuated by SRF overexpression, and miR-664-5p repressed myogenic differentiation by diminishing the accumulation of nuclear ß-catenin. Of note, miR-664-5p's inhibitory effect on myogenic differentiation was abrogated by treatment with Wnt1 protein, the key activator of the Wnt/ß-catenin signaling pathway. Collectively, our findings suggest that miR-664-5p controls SRF and canonical Wnt/ß-catenin signaling pathways in myogenesis.

MiR-127 attenuates adipogenesis by targeting MAPK4 and HOXC6 in porcine adipocytes.

MicroRNAs (miRNAs) have critical roles during adipogenesis; however, their precise functions are not completely understood. Porcine miRNA expression profiles show that miR-127 is dramatically downregulated with age in adipose tissue. We aimed to identify the precise functions and mechanisms of miR-127 in proliferation and adipogenesis. Preadipocytes were cultured under conditions to induce proliferation or differentiation and the effect of miR-127 overexpression on these processes, and the associated bioinformatically predicted target genes, were assessed using luciferase assays, quantitative real-time PCR, western blot analysis, and cell staining techniques. miR-127 increased proliferation by promoting cell cycling, whereas it suppressed differentiation, which was accompanied by reduced lipid accumulation. miR-127 targeted mitogen-activated protein kinase 4 and homeobox C6 (HOXC6) to activate preadipocyte proliferation. During differentiation, miR-127 targeted HOXC6 to attenuate adipogenesis. These findings identify miR-127 as an inhibitor of porcine adipogenesis, which may inform future strategies to reduce porcine fat deposition and treat human obesity.

Dual-Aptamer-Conjugated Molecular Modulator for Detecting Bioactive Metal Ions and Inhibiting Metal-Mediated Protein Aggregation.

Bioactive metal ions play important roles in both physiological and pathological processes. Developing biosensing probes for bioactive metal ion detection can contribute to fields including disease diagnosis and therapy and studying the mechanisms of biological activities. In this work, we designed a dual-aptamer-conjugated molecular modulator that can detect Zn2+ and further inhibit Zn2+-induced amyloid ß (Aß) aggregation. The molecular modulator is able to selectively target Aß species and block Zn2+ due to the specific recognition capability of aptamers. With the binding of Zn2+, the fluorescence signal of this molecular modulator is restored, thus allowing for Zn2+ detection. More importantly, this molecular modulator can inhibit the generation of Zn2+-triggered Aß aggregates due to the trapping of Zn2+ around Aß species. Circular dichroism measurements reveal that the dual-aptamer-conjugated molecular modulator prevents the conformational transition of the Aß monomer from a random coil to a ß-sheet. Furthermore, after treating with the molecular modulator, no Aß aggregate is observed in the Aß solution with added Zn2+, demonstrating that Aß aggregation is successfully inhibited by this molecular modulator. Our approach provides a promising tool for detecting bioactive metal ions and studying the molecular mechanisms behind life activities.

New insights into the structure-performance relationships of mesoporous materials in analytical science.

Mesoporous materials are ideal carriers for guest molecules and they have been widely used in analytical science. The unique mesoporous structure provides special properties including large specific surface area, tunable pore size, and excellent pore connectivity. The structural properties of mesoporous materials have been largely made use of to improve the performance of analytical methods. For instance, the large specific surface area of mesoporous materials can provide abundant active sites and increase the probability of contact between analytes and active sites to produce stronger signals, thus leading to the improvement of detection sensitivity. The connections between analytical performances and the structural properties of mesoporous materials have not been discussed previously. Understanding the "structure-performance relationship" is highly important for the development of analytical methods with excellent performance based on mesoporous materials. In this review, we discuss the structural properties of mesoporous materials that can be optimized to improve the analytical performance. The discussion is divided into five sections according to the analytical performances: (i) selectivity-related structural properties, (ii) sensitivity-related structural properties, (iii) response time-related structural properties, (iv) stability-related structural properties, and (v) recovery time-related structural properties.

Adiponectin AS lncRNA inhibits adipogenesis by transferring from nucleus to cytoplasm and attenuating Adiponectin mRNA translation.

Adiponectin (AdipoQ) is an adipocyte-derived hormone with positive function on systemic glucose and lipid metabolism. Long noncoding RNA (lncRNA) is emerging as a vital regulator of adipogenesis. However, AdipoQ-related lncRNAs in lipid metabolism have not been explored. Here, AdipoQ antisense (AS) lncRNA was first identified, and we further found that it inhibited adipogenesis. The half-life of AdipoQ AS lncRNA was 10 h, whereas that of AdipoQ mRNA was 4 h. During adipogenic differentiation, AdipoQ AS lncRNA translocated from nucleus to cytoplasm. AdipoQ AS lncRNA and AdipoQ mRNA formed an RNA duplex. Moreover, AdipoQ AS lncRNA delivered via injection of adenovirus expressing AdipoQ AS lncRNA decreases white adipose tissue (WAT), brown adipose tissue (BAT) and liver triglycerides (TG) in mice consuming a high fat diet (HFD). Interestingly, the non-overlapping region of AdipoQ AS lncRNA improved serum glucose tolerance and insulin sensitivity in HFD mice, but not AdipoQ AS lncRNA. In conclusion, AdipoQ AS lncRNA transfer from nucleus to cytoplasm inhibits adipogenesis through formation of an AdipoQ AS lncRNA/AdipoQ mRNA duplex to suppress the translation of AdipoQ mRNA. Taken together, we suggest that AdipoQ AS lncRNA is a novel therapeutic target for obesity-related metabolic diseases.

Time-Gated Imaging of Latent Fingerprints and Specific Visualization of Protein Secretions via Molecular Recognition.

Persistent nanophosphors can remain luminescent after excitation ceases; thus, they offer a promising way to avoid background fluorescence interference in bioimaging. In this work, Zn2GeO4:Ga,Mn (ZGO:Ga,Mn) persistent luminescence nanoparticles were developed and they were employed for time-gated imaging of latent fingerprints (LFP). The nanoparticles were functionalized with a carboxyl group and utilized to label LFP through reacting with the amino group in the LFP. Results proved the potent ability of ZGO:Ga,Mn in eliminating background fluorescence to afford highly sensitive LFP imaging. Moreover, LFP aged for 60 days were successfully detected due to the presence of highly stable amino acids. After being functionalized with concanavalin A, the nanoparticles achieved visualization of glycoproteins in LFP. This strategy provides great versatility in LFP imaging and good potential in uncovering the chemical information within LFP, making it valuable in forensic investigations and medical diagnostics.

[Retracted] Long non­coding RNA SNHG6 promotes tumorigenesis in melanoma cells via the microRNA­101­3p/RAP2B axis.

[This retracts the article DOI: 10.3892/ol.2020.12186.].

Real-World Light Field Image Super-Resolution Via Degradation Modulation.

Recent years have witnessed the great advances of deep neural networks (DNNs) in light field (LF) image super-resolution (SR). However, existing DNN-based LF image SR methods are developed on a single fixed degradation (e.g., bicubic downsampling), and thus cannot be applied to super-resolve real LF images with diverse degradation. In this article, we propose a simple yet effective method for real-world LF image SR. In our method, a practical LF degradation model is developed to formulate the degradation process of real LF images. Then, a convolutional neural network is designed to incorporate the degradation prior into the SR process. By training on LF images using our formulated degradation, our network can learn to modulate different degradation while incorporating both spatial and angular information in LF images. Extensive experiments on both synthetically degraded and real-world LF images demonstrate the effectiveness of our method. Compared with existing state-of-the-art single and LF image SR methods, our method achieves superior SR performance under a wide range of degradation, and generalizes better to real LF images. Codes and models are available at https://yingqianwang.github.io/LF-DMnet/.

Latent profiles of bullying perpetration and victimization: Gender differences and family variables.

BACKGROUND: School bullying is a prevalent issue that threatens the psychological and social well-being of adolescents. However, little research has investigated how gender and family variables were related to bullying-involvement patterns among adolescents with siblings. OBJECTIVE: This study explored gender differences in the profiles of bullying involvement and the relationship between sibling, parental variables, and these profiles among Chinese adolescents. PARTICIPANTS AND SETTING: Participants (N = 1,060; 46.0 % boys; Mage = 15.53) were recruited from junior and senior high schools in Jiangxi and Guizhou Provinces, China. METHODS: Bullying involvement, sibling warmth and conflict, and parental psychological maltreatment and neglect were assessed by self-report questionnaire. Latent profile analysis was used to identify subgroups with distinct bullying involvement patterns, then multiple logistic regressions were performed to investigate the associations between family variables and bullying-involvement subgroups. RESULTS: We found gender differences in both the latent profiles of bullying involvement and the associations between profiles and family variables. Only boys were identified severe bully-victims (3.39 %), while only girls were categorized as relational bully-victims (20.18 %). Boys and girls were similarly represented among uninvolved students (70.76 % vs. 66.85 %), moderate bully-victims (15.25 % vs. 6.49 %), and victims (10.59 % vs. 6.49 %). Students with more sibling warmth manifested less likelihood of engaging in bullying-related profiles, with more parental psychological maltreatment, and more parental neglect manifested more likelihood of engaging in bullying-related profiles only among girls. While students with more sibling conflict were related to more bullying-related profiles among boys than girls. CONCLUSIONS: The findings emphasize the importance of developing gender-specific bullying intervention strategies that also consider relevant family factors.

Overexpression of ALDOC Promotes Porcine Intramuscular and Intermuscular Fat Deposition by Activating the AKT-mTORC1 Signaling Pathway.

Skeletal muscle fat accumulation, a common complication of obesity, has garnered increasing attention. For livestock animals, intramuscular fat content is a key determinant of meat quality and directly influences consumer preferences for different meat products. However, genes effectively regulating intramuscular and intermuscular fat (IIMF) deposition remain largely unexplored. To address this gap, we employed transcriptome sequencing of muscle from pigs with high and low IIMF contents, uncovering Aldolase C (ALDOC) as a novel key gene controlling IIMF. ALDOC overexpression significantly enhanced the IIMF content both in vivo and in vitro. Mechanistic investigations revealed that ALDOC activates the AKT-mTORC1 axis to promote lipid accumulation in myotubes and intramuscular adipocytes. Notably, the mTORC1 inhibitor rapamycin abrogated ALDOC's proadipogenic effect. Our findings establish ALDOC as a novel key gene regulating IIMF deposition and identify the ALDOC-AKT-mTORC1 signaling pathway as a promising therapeutic target for treating skeletal muscle fat infiltration and improving pork quality.

Autophagy activation is required for N6-methyladenosine modification to regulate ferroptosis in hepatocellular carcinoma.

BACKGROUND & AIMS: Although ferroptosis holds promise as a new strategy for treating hepatocellular carcinoma (HCC), there are several obstacles that need to be overcome. One major challenge is the lack of understanding about the mechanisms underlying ferroptosis. Additionally, while the m6A modification has been shown to regulate various forms of cell death, its role in regulating ferroptosis in HCC has been largely overlooked. Bridging this knowledge gap, our study aimed to elucidate the regulatory influence of m6A modification on HCC ferroptosis. MATERIALS: Dot blot and EpiQuik m6A RNA Methylation Quantitative kit detected changes in overall m6A modification level during ferroptosis in HCC. MeRIP-qPCR and RIP-qPCR identified that the m6A modification of ATG5 mRNA was significant changed. BALB/c nude mice were used to construct xenograft tumor models to verify the phenotypes upon YTHDC2 silencing. In addition, patient-derived organoid models were used to demonstrate that induction of ferroptosis was an effective strategy against HCC. RESULTS: Our study has shown that inducing ferroptosis is a promising strategy for combatting HCC. Specifically, we have found a significant correlation between ferroptosis and high levels of m6A modification in HCC. Notably, we discovered that the elevation of ATG5 mRNA m6A modification mediated by WTAP is dependent on the reading protein YTHDC2. Importantly, inhibition of either WTAP or YTHDC2 effectively prevented ferroptosis and suppressed HCC development in both in vitro and in vivo models. CONCLUSION: Our study revealed that WTAP upregulates ATG5 expression post-transcriptionally in an m6A-YTHDC2-dependent manner, thereby promoting the translation of ATG5 mRNA during ferroptosis in HCC. These findings have significant implications for the development of innovative and effective therapeutic approaches for HCC treatment.