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On page 1 showing 1 ~ 20 papers out of 36 papers

Salen-Mn compounds induces cell apoptosis in human prostate cancer cells through promoting AMPK activity and cell autophagy.

  • Xiaoshuang Tang‎ et al.
  • Oncotarget‎
  • 2017‎

Currently only docetaxel has been approved to be used in the chemotherapy of prostate cancer and new drugs are urgent need. Salen-Mn is a novel type of synthetic reagent bionic and exerts remarkable anticancer activities. However, the effect of Salen-Mn on human prostate cancer has not been elucidated yet. In this study, we found that treatment of PC-3 and DU145 human prostate cancer cells with Salen-Mn inhibited cell growth in dose and time dependent manner. Moreover, Salen-Mn induced cell apoptosis, and increased the expression of apoptotic proteins, such as cleaved caspase-3, cleaved PARP, and Bax, in PC-3 and DU145 prostate cancer cells. Furthermore, we found that Salen-Mn induced expression of LC3-I/II, which is protein marker of cell autophagy, in both dose and time dependent manners; in addition, Salen-Mn increased the phosphorylation of AMPK, suggesting that Salen-Mn increase cell autophagy through activating AMPK pathway. On the other hand, when PC-3 and DU145 cells were treated with Salen-Mn and 3-MA, an inhibitor of cell autophagy, the inhibitory effect of Salen-Mn on cell growth and the induction of apoptotic proteins were decreased. In addition, we found that Salen-Mn inhibited the growth of PC-3 cell xenografts in nude mice. In summary, our results indicate that Salen-Mn suppresses cell growth through inducing AMPK activity and autophagic cell death related cell apoptosis in prostate cancer cells and suggest that Salen-Mn and its derivatives could be new options for the chemical therapeutics in the treatment of prostate cancer.


Bacterial Communities of the Canola Rhizosphere: Network Analysis Reveals a Core Bacterium Shaping Microbial Interactions.

  • Jean-Baptiste Floc'h‎ et al.
  • Frontiers in microbiology‎
  • 2020‎

The rhizosphere hosts a complex web of prokaryotes interacting with one another that may modulate crucial functions related to plant growth and health. Identifying the key factors structuring the prokaryotic community of the plant rhizosphere is a necessary step toward the enhancement of plant production and crop yield with beneficial associative microorganisms. We used a long-term field experiment conducted at three locations in the Canadian prairies to verify that: (1) the level of cropping system diversity influences the α- and β-diversity of the prokaryotic community of canola (Brassica napus) rhizosphere; (2) the canola rhizosphere community has a stable prokaryotic core; and (3) some highly connected taxa of this community fit the description of hub-taxa. We sampled the rhizosphere of canola grown in monoculture, in a 2-phase rotation (canola-wheat), in a 3-phase rotation (pea-barley-canola), and in a highly diversified 6-phase rotation, five and eight years after cropping system establishment. We detected only one core bacterial Amplicon Sequence Variant (ASV) in the prokaryotic component of the microbiota of canola rhizosphere, a hub taxon identified as cf. Pseudarthrobacter sp. This ASV was also the only hub taxon found in the networks of interactions present in both years and at all three sites. We highlight a cohort of bacteria and archaea that were always connected with the core taxon in the network analyses.


Similar Arbuscular Mycorrhizal Fungal Communities in 31 Durum Wheat Cultivars (Triticum turgidum L. var. durum) Under Field Conditions in Eastern Canada.

  • Franck Stefani‎ et al.
  • Frontiers in plant science‎
  • 2020‎

Wheat is among the important crops harnessed by humans whose breeding efforts resulted in a diversity of genotypes with contrasting traits. The goal of this study was to determine whether different old and new cultivars of durum wheat (Triticum turgidum L. var. durum) recruit specific arbuscular mycorrhizal (AM) fungal communities from indigenous AM fungal populations of soil under field conditions. A historical set of five landraces and 26 durum wheat cultivars were field cultivated in a humid climate in Eastern Canada, under phosphorus-limiting conditions. To characterize the community of AMF inhabiting bulk soil, rhizosphere, and roots, MiSeq amplicon sequencing targeting the 18S rRNA gene (SSU) was performed on total DNAs using a nested PCR approach. Mycorrhizal colonization was estimated using root staining and microscope observations. A total of 317 amplicon sequence variants (ASVs) were identified as belonging to Glomeromycota. The core AM fungal community (i.e., ASVs present in > 50% of the samples) in the soil, rhizosphere, and root included 29, 30, and 29 ASVs, respectively. ASVs from the genera Funneliformis, Claroideoglomus, and Rhizophagus represented 37%, 18.6%, and 14.7% of the sequences recovered in the rarefied dataset, respectively. The two most abundant ASVs had sequence homology with the 18S sequences from well-identified herbarium cultures of Funneliformis mosseae BEG12 and Rhizophagus irregularis DAOM 197198, while the third most abundant ASV was assigned to the genus Paraglomus. Cultivars showed no significant difference of the percentage of root colonization ranging from 57.8% in Arnautka to 84.0% in AC Navigator. Cultivars were generally associated with similar soil, rhizosphere, and root communities, but the abundance of F. mosseae, R. irregularis, and Claroideoglomus sp. sequences varied in Eurostar, Golden Ball, and Wakooma. Although these results were obtained in one field trial using a non-restricted pool of durum wheat and at the time of sampling, that may have filtered the community in biotopes. The low genetic variation between durum wheat cultivars for the diversity of AM symbiosis at the species level suggests breeding resources need not be committed to leveraging plant selective influence through the use of traditional methods for genotype development.


Serum KIAA1199 is an advanced-stage prognostic biomarker and metastatic oncogene in cholangiocarcinoma.

  • Xiangyu Zhai‎ et al.
  • Aging‎
  • 2020‎

Cell proliferation and migration are the determinants of malignant tumor progression, and a better understanding of related genes will lead to the identification of new targets aimed at preventing the spread of cancer. Some studies have shown that KIAA1199 (CEMIP) is a transmembrane protein expressed in many types of noncancerous cells and cancer cells. However, the potential role of KIAA1199 in the progression of cholangiocarcinoma (CCA) remains unclear.


Remarkable Ionic Conductivity in a LZO-SDC Composite for Low-Temperature Solid Oxide Fuel Cells.

  • Zhengwen Tu‎ et al.
  • Nanomaterials (Basel, Switzerland)‎
  • 2021‎

Recently, appreciable ionic conduction has been frequently observed in multifunctional semiconductors, pointing out an unconventional way to develop electrolytes for solid oxide fuel cells (SOFCs). Among them, ZnO and Li-doped ZnO (LZO) have shown great potential. In this study, to further improve the electrolyte capability of LZO, a typical ionic conductor Sm0.2Ce0.8O1.9 (SDC) is introduced to form semiconductor-ionic composites with LZO. The designed LZO-SDC composites with various mass ratios are successfully demonstrated in SOFCs at low operating temperatures, exhibiting a peak power density of 713 mW cm-2 and high open circuit voltages (OCVs) of 1.04 V at 550 °C by the best-performing sample 5LZO-5SDC, which is superior to that of simplex LZO electrolyte SOFC. Our electrochemical and electrical analysis reveals that the composite samples have attained enhanced ionic conduction as compared to pure LZO and SDC, reaching a remarkable ionic conductivity of 0.16 S cm-1 at 550 °C, and shows hybrid H+/O2- conducting capability with predominant H+ conduction. Further investigation in terms of interface inspection manifests that oxygen vacancies are enriched at the hetero-interface between LZO and SDC, which gives rise to the high ionic conductivity of 5LZO-5SDC. Our study thus suggests the tremendous potentials of semiconductor ionic materials and indicates an effective way to develop fast ionic transport in electrolytes for low-temperature SOFCs.


The Specifically Androgen-Regulated Gene (SARG) Promotes Papillary Thyroid Carcinoma (PTC) Lymphatic Metastasis Through Vascular Endothelial Growth Factor C (VEGF-C) and VEGF Receptor 3 (VEGFR-3) Axis.

  • Shuai-Jun Xu‎ et al.
  • Frontiers in oncology‎
  • 2022‎

The papillary thyroid carcinoma (PTC) metastasizes through lymphatic spread, but the follicular thyroid cancer (FTC) metastasis occurs by following hematogenous spread. To date, the molecular mechanism underlying different metastatic routes between PTC and FTC is still unclear. Here, we showed that specifically androgen-regulated gene (SARG) was significantly up-regulated in PTC, while obviously down-regulated in FTC through analyzing the Gene Expression Omnibus (GEO) database. Immunohistochemistry assay verified that the PTC lymph node metastasis was associated with higher levels of SARG protein in clinical PTC patient samples. SARG-knockdown decreased TPC-1 and CGTH-W3 cells viability and migration significantly. On the contrary, SARG-overexpressed PTC cells possessed more aggressive migratory ability and viability. In vivo, SARG overexpression dramatically promoted popliteal lymph node metastasis of xenografts from TPC-1 cells mouse footpad transplanting. Mechanistically, SARG overexpression and knockdown significantly increased and decreased the expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3), respectively, thereby facilitating or inhibiting the tube formation in HUVECs. The tube formation experiment showed that SARG overexpression and knockdown promoted or inhibited the number of tube formations in HUVEC cells, respectively. Taken together, we showed for the first time the differential expression profile of SARG between PTC and FTC, and SARG promotes PTC lymphatic metastasis via VEGF-C/VEGFR-3 signal. It indicates that SARG may represent a target for clinical intervention in lymphatic metastasis of PTC.


Effects of Cirsium setidens (Dunn) Nakai on the osteogenic differentiation of stem cells.

  • Sayan Deb Dutta‎ et al.
  • Molecular medicine reports‎
  • 2021‎

Cirsium setidens (Dunn) Nakai, commonly known as gondre, is a perennial herb that grows predominantly in South Korea. It contains several bioactive phytochemicals with antioxidant, anti‑cancer, anti‑tumor and anti‑inflammatory properties. The present study aimed to investigate the effects of methanolic extracts of gondre on osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). As characterized by nuclear magnetic resonance spectroscopy and matrix‑assisted laser deposition/ionization (time‑of‑flight) mass spectrometry, the methanol extract of gondre was found to be enriched with pectolinarin. After 48 h, enhanced viability of hPDLSCs was observed in the presence of gondre compared with under control conditions, suggesting the biocompatibility of gondre. Notably, biocompatibility was markedly affected by gondre concentration in cultured media. Relatively high cell viability was observed in medium containing 0.05% gondre. Furthermore, mineralization was significantly higher in hPDLSCs in the presence of gondre compared with that in control cells, indicating their mineralization potential. Increased expression of various transcription markers, such as collagen 1, runt‑related transcription factor 2, bone sialoprotein and alkaline phosphatase, was also detected when hPDLSCs were stimulated with gondre compared with in the control groups, further confirming the superior osteogenic potential of gondre extract for tissue engineering applications, particularly in bone tissues.


Loss of LncRNA DUXAP8 synergistically enhanced sorafenib induced ferroptosis in hepatocellular carcinoma via SLC7A11 de-palmitoylation.

  • Zhehao Shi‎ et al.
  • Clinical and translational medicine‎
  • 2023‎

Ferroptosis is an important iron-dependent form of cell death in hepatocellular carcinoma (HCC). Sorafenib, a potent ferroptosis inducer, is used to treat advanced HCC but its efficacy is limited by the development of drug resistance.


Transcriptome profiling of the spl5 mutant reveals that SPL5 has a negative role in the biosynthesis of serotonin for rice disease resistance.

  • Bin Jin‎ et al.
  • Rice (New York, N.Y.)‎
  • 2015‎

Rice mutant, spl5 (spotted leaf 5), has spontaneous hypersensitive-like lesions on its leaves and shows enhanced resistance to pathogens, indicating that SPL5 plays a role in programmed cell death (PCD) and disease resistance. To understand the molecular mechanism of SPL5 gene, we investigated the transcriptome profiles of the spl5 mutant leaves with few lesions (FL) and leaves with many lesions (ML) compared to the wild-type (WT) leaves respectively by microarray.


Oxymatrine downregulates HPV16E7 expression and inhibits cell proliferation in laryngeal squamous cell carcinoma Hep-2 cells in vitro.

  • Xin-Jiang Ying‎ et al.
  • BioMed research international‎
  • 2015‎

To investigate the possible mechanisms of oxymatrine's role in anti laryngeal squamous cell carcinoma.


Source Identification and Apportionment of Trace Elements in Soils in the Yangtze River Delta, China.

  • Shuai Shao‎ et al.
  • International journal of environmental research and public health‎
  • 2018‎

Trace elements pollution has attracted a lot of attention worldwide. However, it is difficult to identify and apportion the sources of multiple element pollutants over large areas because of the considerable spatial complexity and variability in the distribution of trace elements in soil. In this study, we collected total of 2051 topsoil (0⁻20 cm) samples, and analyzed the general pollution status of soils from the Yangtze River Delta, Southeast China. We applied principal component analysis (PCA), a finite mixture distribution model (FMDM), and geostatistical tools to identify and quantitatively apportion the sources of seven kinds of trace elements (chromium (Cr), cadmium (Cd), mercury (Hg), copper (Cu), zinc (Zn), nickel (Ni), and arsenic (As)) in soil. The PCA results indicated that the trace elements in soil in the study area were mainly from natural, multi-pollutant and industrial sources. The FMDM also fitted three sub log-normal distributions. The results from the two models were quite similar: Cr, As, and Ni were mainly from natural sources caused by parent material weathering; Cd, Cu, and Zu were mainly from mixed sources, with a considerable portion from anthropogenic activities such as traffic pollutants, domestic garbage, and agricultural inputs, and Hg was mainly from industrial wastes and pollutants.


Heavy Metal Pollution Delineation Based on Uncertainty in a Coastal Industrial City in the Yangtze River Delta, China.

  • Bifeng Hu‎ et al.
  • International journal of environmental research and public health‎
  • 2018‎

Assessing heavy metal pollution and delineating pollution are the bases for evaluating pollution and determining a cost-effective remediation plan. Most existing studies are based on the spatial distribution of pollutants but ignore related uncertainty. In this study, eight heavy-metal concentrations (Cr, Pb, Cd, Hg, Zn, Cu, Ni, and Zn) were collected at 1040 sampling sites in a coastal industrial city in the Yangtze River Delta, China. The single pollution index (PI) and Nemerow integrated pollution index (NIPI) were calculated for every surface sample (0-20 cm) to assess the degree of heavy metal pollution. Ordinary kriging (OK) was used to map the spatial distribution of heavy metals content and NIPI. Then, we delineated composite heavy metal contamination based on the uncertainty produced by indicator kriging (IK). The results showed that mean values of all PIs and NIPIs were at safe levels. Heavy metals were most accumulated in the central portion of the study area. Based on IK, the spatial probability of composite heavy metal pollution was computed. The probability of composite contamination in the central core urban area was highest. A probability of 0.6 was found as the optimum probability threshold to delineate polluted areas from unpolluted areas for integrative heavy metal contamination. Results of pollution delineation based on uncertainty showed the proportion of false negative error areas was 6.34%, while the proportion of false positive error areas was 0.86%. The accuracy of the classification was 92.80%. This indicated the method we developed is a valuable tool for delineating heavy metal pollution.


Arbuscular Mycorrhizal Symbiosis Alleviates Salt Stress in Black Locust through Improved Photosynthesis, Water Status, and K+/Na+ Homeostasis.

  • Jie Chen‎ et al.
  • Frontiers in plant science‎
  • 2017‎

Soil salinization and the associated land degradation are major and growing ecological problems. Excess salt in soil impedes plant photosynthetic processes and root uptake of water and nutrients such as K+. Arbuscular mycorrhizal (AM) fungi can mitigate salt stress in host plants. Although, numerous studies demonstrate that photosynthesis and water status are improved by mycorrhizae, the molecular mechanisms involved have received little research attention. In the present study, we analyzed the effects of AM symbiosis and salt stress on photosynthesis, water status, concentrations of Na+ and K+, and the expression of several genes associated with photosynthesis (RppsbA, RppsbD, RprbcL, and RprbcS) and genes coding for aquaporins or membrane transport proteins involved in K+ and/or Na+ uptake, translocation, or compartmentalization homeostasis (RpSOS1, RpHKT1, RpNHX1, and RpSKOR) in black locust. The results showed that salinity reduced the net photosynthetic rate, stomatal conductance, and relative water content in both non-mycorrhizal (NM) and AM plants; the reductions of these three parameters were less in AM plants compared with NM plants. Under saline conditions, AM fungi significantly improved the net photosynthetic rate, quantum efficiency of photosystem II photochemistry, and K+ content in plants, but evidently reduced the Na+ content. AM plants also displayed a significant increase in the relative water content and an evident decrease in the shoot/root ratio of Na+ in the presence of 200 mM NaCl compared with NM plants. Additionally, mycorrhizal colonization upregulated the expression of three chloroplast genes (RppsbA, RppsbD, and RprbcL) in leaves, and three genes (RpSOS1, RpHKT1, and RpSKOR) encoding membrane transport proteins involved in K+/Na+ homeostasis in roots. Expression of several aquaporin genes was regulated by AM symbiosis in both leaves and roots depending on soil salinity. This study suggests that the beneficial effects of AM symbiosis on the photosynthetic capacity, water status, and K+/Na+ homeostasis lead to the improved growth performance and salt tolerance of black locust exposed to salt stress.


Efficacy and safety of tuina for senile insomnia: A protocol for systematic review and meta-analysis.

  • Yangshengjie Liu‎ et al.
  • Medicine‎
  • 2022‎

Insomnia is a common diseases of the elderly, tuina is a widely used treatment. At present, there is a lack of supportive evidence on efficacy and safety of tuina for senile insomnia. The purpose of this systematic review is to assess the effectiveness and safety of tuina therapy in the treatment of senile insomnia.


Ferroptosis-Related Long Noncoding RNAs Have Excellent Predictive Ability for Multiomic Characteristics of Bladder Cancer.

  • Jingchao Liu‎ et al.
  • Oxidative medicine and cellular longevity‎
  • 2022‎

The role of ferroptosis-related long non-coding RNAs (lncRNAs) in bladder cancer remains elusive. This study is aimed at examining the prognostic role of ferroptosis-related lncRNAs in bladder cancer.


Risk stratification by long non-coding RNAs profiling in COVID-19 patients.

  • Jie Cheng‎ et al.
  • Journal of cellular and molecular medicine‎
  • 2021‎

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic worldwide. Long non-coding RNAs (lncRNAs) are a subclass of endogenous, non-protein-coding RNA, which lacks an open reading frame and is more than 200 nucleotides in length. However, the functions for lncRNAs in COVID-19 have not been unravelled. The present study aimed at identifying the related lncRNAs based on RNA sequencing of peripheral blood mononuclear cells from patients with SARS-CoV-2 infection as well as health individuals. Overall, 17 severe, 12 non-severe patients and 10 healthy controls were enrolled in this study. Firstly, we reported some altered lncRNAs between severe, non-severe COVID-19 patients and healthy controls. Next, we developed a 7-lncRNA panel with a good differential ability between severe and non-severe COVID-19 patients using least absolute shrinkage and selection operator regression. Finally, we observed that COVID-19 is a heterogeneous disease among which severe COVID-19 patients have two subtypes with similar risk score and immune score based on lncRNA panel using iCluster algorithm. As the roles of lncRNAs in COVID-19 have not yet been fully identified and understood, our analysis should provide valuable resource and information for the future studies.


Long-Term Land Use Affects Phosphorus Speciation and the Composition of Phosphorus Cycling Genes in Agricultural Soils.

  • Jin Liu‎ et al.
  • Frontiers in microbiology‎
  • 2018‎

Agriculturally-driven land transformation is increasing globally. Improving phosphorus (P) use efficiency to sustain optimum productivity in diverse ecosystems, based on knowledge of soil P dynamics, is also globally important in light of potential shortages of rock phosphate to manufacture P fertilizer. We investigated P chemical speciation and P cycling with solution 31P nuclear magnetic resonance, P K-edge X-ray absorption near-edge structure spectroscopy, phosphatase activity assays, and shotgun metagenomics in soil samples from long-term agricultural fields containing four different land-use types (native and tame grasslands, annual croplands, and roadside ditches). Across these land use types, native and tame grasslands showed high accumulation of organic P, principally orthophosphate monoesters, and high acid phosphomonoesterase activity but the lowest abundance of P cycling genes. The proportion of inositol hexaphosphates (IHP), especially the neo-IHP stereoisomer that likely originates from microbes rather than plants, was significantly increased in native grasslands than croplands. Annual croplands had the largest variances of soil P composition, and the highest potential capacity for P cycling processes based on the abundance of genes coding for P cycling processes. In contrast, roadside soils had the highest soil Olsen-P concentrations, lowest organic P, and highest tricalcium phosphate concentrations, which were likely facilitated by the neutral pH and high exchangeable Ca of these soils. Redundancy analysis demonstrated that IHP by NMR, potential phosphatase activity, Olsen-P, and pH were important P chemistry predictors of the P cycling bacterial community and functional gene composition. Combining chemical and metagenomics results provides important insights into soil P processes and dynamics in different land-use ecosystems.


Why does oriental arborvitae grow better when mixed with black locust: Insight on nutrient cycling?

  • Xuedong Chen‎ et al.
  • Ecology and evolution‎
  • 2018‎

To identify why tree growth differs by afforestation type is a matter of prime concern in forestry. A study was conducted to determine why oriental arborvitae (Platycladus orientalis) grows better in the presence of black locust (Robinia pseudoacacia) than in monoculture. Different types of stands (i.e., monocultures and mixture of black locust and oriental arborvitae, and native grassland as a control) were selected in the Loess Plateau, China. The height and diameter at breast height of each tree species were measured, and soil, shoot, and root samples were sampled. The arbuscular mycorrhizal (AM) attributes, shoot and root nutrient status, height and diameter of black locust were not influenced by the presence of oriental arborvitae. For oriental arborvitae, however, growing in mixture increased height and diameter and reduced shoot Mn, Ca, and Mg contents, AM fungal spore density, and colonization rate. Major changes in soil properties also occurred, primarily in soil water, NO 3-N, and available K levels and in soil enzyme activity. The increase in soil water, N, and K availability in the presence of black locust stimulated oriental arborvitae growth, and black locust in the mixed stand seems to suppress the development of AM symbiosis in oriental arborvitae roots, especially the production of AM fungal spores and vesicles, through improving soil water and N levels, thus freeing up carbon to fuel plant growth. Overall, the presence of black locust favored oriental arborvitae growth directly by improving soil water and fertility and indirectly by repressing AM symbiosis in oriental arborvitae roots.


Overexpression of HMGA1 confers radioresistance by transactivating RAD51 in cholangiocarcinoma.

  • Jianping Song‎ et al.
  • Cell death discovery‎
  • 2021‎

Cholangiocarcinomas (CCAs) are rare but aggressive tumors of the bile ducts. CCAs are often diagnosed at an advanced stage and respond poorly to current conventional radiotherapy and chemotherapy. High mobility group A1 (HMGA1) is an architectural transcription factor that is overexpressed in multiple malignant tumors. In this study, we showed that the expression of HMGA1 is frequently elevated in CCAs and that the high expression of this gene is associated with a poor prognosis. Functionally, HMGA1 promotes CCA cell proliferation/invasion and xenograft tumor growth. Furthermore, HMGA1 transcriptionally activates RAD51 by binding to its promoter through two HMGA1 response elements. Notably, overexpression of HMGA1 promotes radioresistance whereas its knockdown causes radiosensitivity of CCA cells to X-ray irradiation. Moreover, rescue experiments reveal that inhibition of RAD51 reverses the effect of HMGA1 on radioresistance and proliferation/invasion. These findings suggest that HMGA1 functions as a novel regulator of RAD51 and confers radioresistance in cholangiocarcinoma.


MELK promotes HCC carcinogenesis through modulating cuproptosis-related gene DLAT-mediated mitochondrial function.

  • Zhipeng Li‎ et al.
  • Cell death & disease‎
  • 2023‎

Cuproptosis caused by copper overload is mediated by a novel regulatory mechanism that differs from previously documented mechanisms regulating cell death. Cells dependent on mitochondrial respiration showed increased sensitivity to a copper ionophore elesclomol that induced cuproptosis. Maternal embryonic leucine zipper kinase(MELK) promotes tumorigenesis and tumor progression through the PI3K/mTOR pathway, which exerts its effects partly by targeting the pyruvate dehydrogenase complex(PDHc) and reprogramming the morphology and function of mitochondria. However, the role of MELK in cuproptosis remains unclear. Here, we validated that elevated MELK expression enhanced the activity of PI3K/mTOR signaling and subsequently promoted Dihydrolipoamide S-Acetyltransferase (DLAT) expression and stabilized mitochondrial function. This regulatory effect helped to improve mitochondrial respiration, eliminate excessive intracellular reactive oxygen species (ROS), reduce intracellular oxidative stress/damage and the possibility of mitochondria-induced cell fate alternations, and ultimately promote the progression of HCC. Meanwhile, elesclomol reduced translocase of outer mitochondrial membrane 20(TOM 20) expression and increased DLAT oligomers. Moreover, the above changes of MELK to HCC were abolished by elesclomol. In conclusion, MELK enhanced the levels of the cuproptosis-related signature(CRS) gene DLAT (especially the proportion of DLAT monomer) by activating the PI3K/mTOR pathway, thereby promoting elesclomol drug resistance, altering mitochondrial function, and ultimately promoting HCC progression.


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