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Journal of Cellular Physiology Dec 2023Glucose metabolic reprogramming, known as the Warburg effect, is one of the metabolic hallmarks of tumor cells. Cancer cells preferentially metabolize glucose by...
Glucose metabolic reprogramming, known as the Warburg effect, is one of the metabolic hallmarks of tumor cells. Cancer cells preferentially metabolize glucose by glycolysis rather than mitochondrial oxidative phosphorylation regardless of oxygen availability, but the regulatory mechanism underlying this switch has been incompletely understood. Here, we report that the circular RNA circ ankyrin repeat domain 17 (ANKRD17) functions as a key regulator for glycolysis to promote cell growth, migration, invasion, and cell-cycle progression in breast cancer (BC) cells. We further show that circANKRD17 acts to accelerate glycolysis in BC cells by acting as a sponge for miR-143 and in turn overrides the repressive effect of miR-143, a well-documented glycolytic repressor, on hexokinase 2 in BC cells, thus resulting in enhanced glycolysis in BC cells. These data suggest the circANKRD17-miR-143 cascade as a novel mechanism in controlling glucose metabolic reprogramming in BC cells and suggest circANKRD17 as a promising therapeutic target to interrupt cancerous glycolysis.
Topics: Humans; Female; MicroRNAs; Breast Neoplasms; Cell Line, Tumor; Glycolysis; Cell Proliferation; Glucose; RNA-Binding Proteins
PubMed: 37812578
DOI: 10.1002/jcp.31128 -
Biochemical Pharmacology Aug 2023Circular RNAs (circRNAs), a subclass of noncoding RNAs, have been demonstrated to play an essential role in osteosarcoma (OS) development. However, there is still a...
Circular RNAs (circRNAs), a subclass of noncoding RNAs, have been demonstrated to play an essential role in osteosarcoma (OS) development. However, there is still a significant gap in investigating its biological functions and underlying molecular mechanisms, and novel targets of circRNAs have yet to be fully explored. Herein, we found that hsa_circ_0007031 is noticeably raised in OS clinical tissues and cell lines. Hsa_circ_0007031 accelerates OS cell proliferation and migration in vitro and tumor growth and metastasis in vivo and is strongly linked with the stemness of cancer stem cells in OS. Mechanistically, hsa_circ_0007031 shares miRNA response elements with Homeobox B6 (HOXB6), which is identified as a novel pro-tumorigenic gene of OS. Hsa_circ_0007031 competitively binds to miR-196a-5p to prevent miR-196a-5p from lowering the level of HOXB6, which modulates chemokines of cytokine-cytokine receptor interaction signaling pathway and finally promotes OS malignant behavior. In summary, our data unveiled that hsa_circ_0007031/miR-196a-5p/HOXB6 axis-mediated cytokine-cytokine receptor interaction facilitates the progression of OS and maintains the properties of tumor stem cells, which could be a promising therapeutic target for OS.
Topics: Humans; RNA, Circular; Genes, Homeobox; Gene Expression Regulation, Neoplastic; MicroRNAs; Cell Proliferation; Osteosarcoma; Bone Neoplasms; Cell Line, Tumor; Homeodomain Proteins
PubMed: 37356630
DOI: 10.1016/j.bcp.2023.115667 -
Cell Metabolism Apr 2024The finding that animals with circadian gene mutations exhibit diet-induced obesity and metabolic syndrome with hypoinsulinemia revealed a distinct role for the clock in... (Review)
Review
The finding that animals with circadian gene mutations exhibit diet-induced obesity and metabolic syndrome with hypoinsulinemia revealed a distinct role for the clock in the brain and peripheral tissues. Obesogenic diets disrupt rhythmic sleep/wake patterns, feeding behavior, and transcriptional networks, showing that metabolic signals reciprocally control the clock. Providing access to high-fat diet only during the sleep phase (light period) in mice accelerates weight gain, whereas isocaloric time-restricted feeding during the active period enhances energy expenditure due to circadian induction of adipose thermogenesis. This perspective focuses on advances and unanswered questions in understanding the interorgan circadian control of healthful metabolism.
Topics: Mice; Animals; Obesity; Weight Gain; Periodicity; Adiposity; Metabolic Syndrome; Energy Metabolism; Circadian Rhythm; Circadian Clocks
PubMed: 38335957
DOI: 10.1016/j.cmet.2024.01.009 -
Journal of Sleep Research Aug 2023The study objective was to explore associations of fetal and infant weight patterns and preterm birth with sleep and 24-h activity rhythm parameters at school-age. In...
The study objective was to explore associations of fetal and infant weight patterns and preterm birth with sleep and 24-h activity rhythm parameters at school-age. In our prospective population-based study, 1327 children were followed from birth to age 10-15 years. Fetal weight was estimated using ultrasound in the second and third trimester of pregnancy. Birth weight and gestational age were available from midwife registries. Infant weight was measured at 6, 12 and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change of >0.67 standard deviation between the corresponding age intervals. At school-age, sleep duration, sleep efficiency, wake after sleep onset, social jetlag, inter-daily stability, and intra-daily variability were assessed using tri-axial wrist actigraphy for 9 consecutive nights. We observed that low birth weight (<2500 g) was associated with 0.24 standard deviation (95% confidence interval [CI] 0.04; 0.43) longer sleep duration compared to normal weight. Compared to normal growth, growth deceleration in fetal life and infancy was associated with 0.40 standard deviation (95% CI 0.07; 0.73) longer sleep duration, 0.44 standard deviation (95% CI 0.14; 0.73) higher sleep efficiency, and -0.41 standard deviation (95% CI -0.76; -0.07) shorter wake after sleep onset. A pattern of normal fetal growth followed by infant growth acceleration was associated with -0.40 standard deviation (95% CI -0.61; -0.19) lower inter-daily stability. Preterm birth was not associated with any sleep or 24-h rhythm parameters. Our findings showed that children with fetal and infant growth restriction had longer and more efficient sleep at school-age, which may be indicative of an increased need for sleep for maturational processes and development after a difficult start in life.
Topics: Infant, Newborn; Female; Pregnancy; Infant; Child; Humans; Adolescent; Prospective Studies; Infant, Low Birth Weight; Gestational Age; Child Development; Sleep; Birth Weight
PubMed: 36707974
DOI: 10.1111/jsr.13822 -
Pharmaceutical Biology Dec 2024Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity.
CONTEXT
Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity.
OBJECTIVE
This study synthesizes PPT derivatives to assess their anticancer activities.
MATERIALS AND METHODS
Compounds E1-E16 antiproliferative activity was tested against four human cancer cell lines (H446, MCF-7, HeLa, A549) and two normal cell lines (L02, BEAS-2B) using the CCK-8 assay. The effects of compound on A549 cell growth were evaluated through molecular docking, assays (flow cytometry, wound healing, Transwell, colony formation, Western blot), and tests in female BALB/c nude mice treated with (2 and 4 mg/kg). (4 mg/kg) significantly reduced xenograft tumor growth compared to the DMSO control group.
RESULTS
Among the 16 PPT derivatives tested for cytotoxicity, exhibited potent effects against A549 cells (IC: 0.35 ± 0.13 µM) and exceeded the reference drugs PPT and etoposide to inhibit the growth of xenograft tumours. -induced cell cycle arrest in the S and G2/M phases accelerated tubulin depolymerization and triggered apoptosis and mitochondrial depolarization while regulating the expression of apoptosis-related proteins and effectively inhibited cell migration and invasion, suggesting a potential to limit metastasis. Molecular docking showed binding of to tubulin at the colchicine site and to Akt, with a consequent down-regulation of PI3K/Akt pathway proteins.
DISCUSSION AND CONCLUSIONS
This research lays the groundwork for advancing cancer treatment through developing and using PPT derivatives. The encouraging results associated with call for extended research and clinical validation, leading to novel and more effective cancer therapies.
Topics: Mice; Animals; Humans; Female; Podophyllotoxin; Tubulin; Molecular Docking Simulation; Mice, Nude; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Drug Screening Assays, Antitumor; Antineoplastic Agents; Cell Proliferation; Cell Line, Tumor; Apoptosis; Tubulin Modulators
PubMed: 38393642
DOI: 10.1080/13880209.2024.2318350 -
Carcinogenesis Aug 2023Circular RNAs (circRNAs) have been accepted to play key roles in the development and progression of mutiple cancers including colorectal cancer (CRC). Here, we...
Circular RNAs (circRNAs) have been accepted to play key roles in the development and progression of mutiple cancers including colorectal cancer (CRC). Here, we identified circ-METTL9, derived from 2 to 4 exons of METTL9 gene, may promote CRC progression by accelerating cell cycle progression. However, the role and mechanism of circ-METTL9 in CRC remains unclear. Based on our data, the expression of circ-METTL9 was significantly upregulated in CRC tissues and markedly increased in advanced tumors in CRC patients. Functional experiments demonstrated that circ-METTL9 overexpression promoted CRC cells proliferation and migration in vitro, and simultaneously enhanced CRC tumor growth and metastasis in vivo. Mechanistically, RNA immunoprecipitation (RIP) assays proved that circ-METTL9 might be a miRNA sponge, and RNA pulldown assays showed the interaction between circ-METTL9 and miR-551b-5p. Notably, cyclin-dependent kinase 6 (CDK6), a key regulator in cell cycle, is a conserved downstream target of miR-551b-5p. Taken together, our findings highlight a novel oncogenic function of circ-METTL9 in CRC progression via circ-METTL9/miR-551b-5p/CDK6 axis, which may serve as a prognostic biomarker and therapeutic target for CRC patients.
Topics: Humans; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Cyclin-Dependent Kinase 6; MicroRNAs; RNA, Circular; Methyltransferases
PubMed: 37158456
DOI: 10.1093/carcin/bgad031 -
Frontiers in Endocrinology 2023Sex differences in prenatal growth may contribute to sex-dependent programming effects on postnatal phenotype.
INTRODUCTION
Sex differences in prenatal growth may contribute to sex-dependent programming effects on postnatal phenotype.
METHODS
We integrated for the first time phenotypic, histomorphological, clinico-chemical, endocrine and gene expression analyses in a single species, the bovine conceptus at mid-gestation.
RESULTS
We demonstrate that by mid-gestation, before the onset of accelerated growth, the female conceptus displays asymmetric lower growth compared to males. Female fetuses were smaller with lower ponderal index and organ weights than males. However, their brain:body weight, brain:liver weight and heart:body weight ratios were higher than in males, indicating brain and heart 'sparing'. The female placenta weighed less and had lower volumes of trophoblast and fetal connective tissue than the male placenta. Female umbilical cord vessel diameters were smaller, and female-specific relationships of body weight and brain:liver weight ratios with cord vessel diameters indicated that the umbilico-placental vascular system creates a growth-limiting environment where blood flow is redistributed to protect brain and heart growth. Clinico-chemical indicators of liver perfusion support this female-specific growth-limiting phenotype, while lower insulin-like growth factor 2 (IGF2) gene expression in brain and heart, and lower circulating IGF2, implicate female-specific modulation of key endocrine mediators by nutrient supply.
CONCLUSION
This mode of female development may increase resilience to environmental perturbations and contribute to sex-bias in programming outcomes including susceptibility to non-communicable diseases.
Topics: Pregnancy; Female; Male; Animals; Cattle; Placenta; Fetus; Trophoblasts; Liver; Body Weight
PubMed: 38362586
DOI: 10.3389/fendo.2023.1306513 -
Nature Communications Sep 2023Most growth references for very preterm infants were developed using measurements taken at birth, and were thought to represent intrauterine growth. However, it remains...
Most growth references for very preterm infants were developed using measurements taken at birth, and were thought to represent intrauterine growth. However, it remains unclear whether the goal of approximating an intrauterine growth rate as stated by the American Academy of Pediatrics is attainable by very preterm infants. Using real-world measurement data from very preterm infants born between 2010 through 2020, we develop models to characterize the patterns of postnatal growth, and compare them to intrauterine growth. By assessing the weight growth rate, we show three phases of postnatal growth not evident in intrauterine growth. Furthermore, postnatal length and head circumference growth exhibit a slow rate after birth, followed by an acceleration. Collectively, postnatal and intrauterine growth are distinctly different. Although postnatal growth models do not represent optimal growth of very preterm infants, they can serve as a practical tool for clinical assessment of growth and for nutrition research.
Topics: Infant, Newborn; Infant; Humans; Child; Infant, Premature; Anthropometry; Acceleration
PubMed: 37726287
DOI: 10.1038/s41467-023-41069-0 -
British Journal of Haematology Aug 2023Multiple myeloma (MM) is the second most common haematological malignancy. Despite the development of new drugs and treatments in recent years, the therapeutic outcomes...
Multiple myeloma (MM) is the second most common haematological malignancy. Despite the development of new drugs and treatments in recent years, the therapeutic outcomes of patients are not satisfactory. It is necessary to further investigate the molecular mechanism underlying MM progression. Herein, we found that high E2F2 expression was correlated with poor overall survival and advanced clinical stages in MM patients. Gain- and loss-of-function studies showed that E2F2 inhibited cell adhesion and consequently activated cell epithelial-to-mesenchymal transition (EMT) and migration. Further experiments revealed that E2F2 interacted with the PECAM1 promoter to suppress its transcriptional activity. The E2F2-knockdown-mediated promotion of cell adhesion was significantly reversed by the repression of PECAM1 expression. Finally, we observed that silencing E2F2 significantly inhibited viability and tumour progression in MM cell models and xenograft mouse models respectively. This study demonstrates that E2F2 plays a vital role as a tumour accelerator by inhibiting PECAM1-dependent cell adhesion and accelerating MM cell proliferation. Therefore, E2F2 may serve as a potential independent prognostic marker and therapeutic target for MM.
Topics: Humans; Animals; Mice; Multiple Myeloma; Platelet Endothelial Cell Adhesion Molecule-1; Cell Adhesion; Cell Line, Tumor; Gene Expression Regulation; Cell Proliferation; E2F2 Transcription Factor
PubMed: 37365680
DOI: 10.1111/bjh.18958 -
Stem Cell Research & Therapy Sep 2023Inflammatory memory or trained immunity is a recently described process in immune and non-immune tissue resident cells, whereby previous exposure to inflammation...
BACKGROUND
Inflammatory memory or trained immunity is a recently described process in immune and non-immune tissue resident cells, whereby previous exposure to inflammation mediators leads to a faster and stronger responses upon secondary challenge. Whether previous muscle injury is associated with altered responses to subsequent injury by satellite cells (SCs), the muscle stem cells, is not known.
METHODS
We used a mouse model of repeated muscle injury, in which intramuscular cardiotoxin (CTX) injections were administered 50 days apart in order to allow for full recovery of the injured muscle before the second injury. The effect of prior injury on the phenotype, proliferation and regenerative potential of satellite cells following a second injury was examined in vitro and in vivo by immunohistochemistry, RT-qPCR and histological analysis.
RESULTS
We show that SCs isolated from muscle at 50 days post-injury (injury-experienced SCs (ieSCs)) enter the cell cycle faster and form bigger myotubes when cultured in vitro, compared to control SCs isolated from uninjured contralateral muscle. Injury-experienced SCs were characterized by the activation of the mTORC 1 signaling pathway, suggesting they are poised to activate sooner following a second injury. Consequently, upon second injury, SCs accumulate in greater numbers in muscle at 3 and 10 days after injury. These changes in SC phenotype and behavior were associated with accelerated muscle regeneration, as evidenced by an earlier appearance of bigger fibers and increased number of myonuclei per fiber at day 10 after the second injury.
CONCLUSIONS
Overall, we show that skeletal muscle injury has a lasting effect on SC function priming them to respond faster to a subsequent injury. The ieSCs have long-term enhanced regenerative properties that contribute to accelerated regeneration following a secondary challenge.
Topics: Animals; Mice; Reinjuries; Muscle Fibers, Skeletal; Muscle, Skeletal; Cell Cycle; Cell Division
PubMed: 37697344
DOI: 10.1186/s13287-023-03492-4