Objective: A pentacyclic triterpene, oleanolic acid (OA), has anti-inflammatory activity. The role of oleanolic acid in aging is poorly understood, and the regulatory mechanism of IGF-1 signaling in aging is still not fully understood. Thus, we hypothesized that OA could delay aging by regulating the PI3K/AKT/mTOR pathway via insulin-like growth factor-1 (IGF-1).
View Article and Find Full Text PDFGemcitabine serves as a first-line chemotherapeutic treatment for pancreatic cancer (PC), but it is prone to rapid drug resistance. Increasing the sensitivity of PC to gemcitabine has long been a focus of research. Fasting interventions may augment the effects of chemotherapy and present new options.
View Article and Find Full Text PDFPurpose: Wet AMD (wAMD) is associated with cellular senescence. However, senescent cell-targeted therapies for wAMD have rarely been comprehensively studied. This study aimed to explore the therapeutic effects of senolytic agents on choroidal neovascularization (CNV).
View Article and Find Full Text PDFObjective: The temporomandibular joint (TMJ) disc cushions intraarticular stress during mandibular movements. While mechanical overloading is related to cartilage degeneration, the pathogenesis of TMJ disc degeneration is unclear. Here, we determined the regulatory role of mechanoinductive transient receptor potential vanilloid 4 (TRPV4) in mechanical overload-induced TMJ disc degeneration.
View Article and Find Full Text PDFSenescent cells accumulate in aged organisms and promote the progression of age-related diseases including cataracts. Therefore, we aimed to study the therapeutic effects of senescence-targeting drugs on cataracts. In this study, a 28-day D-galactose-induced cataract rat model was used.
View Article and Find Full Text PDFBackground: Cell competition is an important feature in pancreatic cancer (PC) progression, but the underlying mechanism remains elusive. This study aims to explore the role of exosomes derived from normal pancreatic ductal epithelial cells involved in PC progression.
Methods: PC cells and pancreatic stellate cells (PSCs) were treated with exosomes isolated from pancreatic ductal epithelial cells.
Oncogenic processes exert their greatest effect by targeting regulators of cell proliferation. Studying the mechanism underlying growth augmentation is expected to improve clinical therapies. The ovarian tumor (OTU) subfamily deubiquitinases have been implicated in the regulation of critical cell-signaling cascades, but most OTUs functions remain to be investigated.
View Article and Find Full Text PDFThe Cyclin-Dependent Kinase Inhibitor p16 (p16) acts as a tumor suppressor in most cells, but for HPV transformed cervical cancer, in which oncoprotein E7 expressed by human papillomavirus (HPV) mediates the degradation of retinoblastoma protein (Rb), p16 exhibits oncogenic activity. Our study was conducted to study the mechanism underling p16 mediated promoting effect of cell proliferation in cervical cancer cell lines. CCK8 assay and EdU incorporation were conducted to evaluate cell proliferation.
View Article and Find Full Text PDF: DOT1L regulates various genes involved in cancer onset and progression by catalyzing H3K79 methylation, but how DOT1L activity itself is regulated is unclear. Here, we aimed to identify specific DOT1L post-translational modifications that might regulate DOT1L activity and thus impact on colorectal cancer (CRC) progression. : We conducted affinity purification and mass spectrometry to explore DOT1L post-translational modifications.
View Article and Find Full Text PDFBACKGROUND The oncogene PIM1, encoding a constitutively active serine/threonine protein kinase, is involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. There is a growing body of literature on the role of PIM1-mediated cellular senescence, but the precise mechanism remains unclear. MATERIAL AND METHODS Silver staining and LC-MS/MS analysis were performed to investigate the protein interacting with PIM1.
View Article and Find Full Text PDFCell Mol Life Sci
October 2019
The ability of cells to repair DNA double-strand breaks (DSBs) is important for maintaining genome stability and eliminating oncogenic DNA lesions. Two distinct and complementary pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are employed by mammalian cells to repair DNA DSBs. Each pathway is tightly controlled in response to increased DSBs.
View Article and Find Full Text PDFp53 is an essential tumor suppressor, whose activity is finely tuned by the posttranslational modifications. Previous research has reported that β-hydroxybutyrate (BHB) induces β-hydroxybutyrylation (Kbhb), which is a novel histone posttranslational modification. Here we report that p53 is modified by kbhb and that this modification occurs at lysines 120, 319, and 370 of p53.
View Article and Find Full Text PDFBiochem Biophys Res Commun
September 2018
TIMELESS protein is known to be essential for normal circadian rhythms. Aging is a deleterious process which affects all the physiological functions of complex organisms including the circadian rhythms. The circadian aging may produce disorganization among the circadian rhythms, arrhythmicity and even, disconnection from the environment, resulting in a detrimental situation to the organism.
View Article and Find Full Text PDFAutophagy is a protein degradation process by which intracellular materials are recycled for energy homeostasis. However, the metabolic status and energy source of autophagy-defective tumor cells are poorly understood. Here, our data show that amino acid uptake from the extracellular environment is increased in autophagy-deficient cells upon glutamine deprivation.
View Article and Find Full Text PDFBiochem Biophys Res Commun
June 2018
The proto-oncogene PIM1 encodes Ser/Thr kinase and regulates cell growth, differentiation and apoptosis. However, more and more studies including ours have found that PIM1 can induce senescence in normal human diploid fibroblasts and behave as a tumor suppressor. But the relevant molecular mechanism of this process is not yet clear.
View Article and Find Full Text PDFP16 is the product of cyclin-dependent kinase 2 (CDKN2A) gene and plays multi-pronged roles in the cancer progression. Breast cancer (BC) is the most commonly diagnosed cancer type among females. In the current study, the potential function of P16 in the growth and metastasis of BC was investigated.
View Article and Find Full Text PDFAndrogens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex.
View Article and Find Full Text PDFParkin, a ubiquitin E3 ligase, is mutated in most cases of autosomal recessive early onset Parkinson disease. It was discovered that Parkin is also mutated in glioblastoma and other human malignancies and that it inhibits tumor cell growth. Here, we identified pyruvate kinase M2 (PKM2) as a unique substrate for parkin through biochemical purification.
View Article and Find Full Text PDFUbiquitin modification at double strand breaks (DSB) sites is an essential regulator of signaling and repair. γH2AX extends from DSB sites and provides a platform for subsequent recruitment and amplification of DNA repair proteins and signaling factors. Here, we found that RNF8/RNF168 ubiquitylates γH2AX.
View Article and Find Full Text PDFLong non-coding RNAs (lncRNAs) have recently emerged as key players in many physiologic and pathologic processes. Although many lncRNAs have been identified, few lncRNAs have been characterized functionally in aging. In this study, we used human fibroblast cells to investigate genome-wide lncRNA expression during cellular senescence.
View Article and Find Full Text PDFUnlabelled: Cellular senescence is a state of permanent cellular arrest that provides an initial barrier to cell transformation and tumorigenesis. In this study, we report that expression of
Nad(p)h: quinone oxidoreductase 1 (NQO1), a cytoplasmic 2-electron reductase, is induced during oncogene-induced senescence (OIS). Depletion of NQO1 resulted in the delayed onset of senescence.
Calcium and calcium channels are closely related to the estrogen-induced nongenomic effect of endometrial carcinoma, but the specific role of calcium channels is unknown. This study aimed to explore the expression and the biologic effect of the L-type calcium channel in endometrial carcinoma cells and to clarify the molecular mechanism of the relationship between L-type calcium channels and estrogen. The immunohistochemical results showed that Ca(2+) channel subunit α 1D (Cav1.
View Article and Find Full Text PDFTo study the mechanisms underlying the IL-6-promoted angiogenic microenvironment in EGFRvIII-positive glioblastoma, VEGF expression in EGFRvIII-positive/negative tumors was determined by optical molecular imaging. Next, the HUVEC tube formation assay, Western blot, qPCR, RNA silencing, chromatin immunoprecipitation, luciferase reporter and ELISA assays were performed to examine the role of IL-6 and C/EBPβ in the formation of the angiogenic microenvironment in EGFRvIII-positive tumors. Finally, in vitro and in vivo genistein treatment experiments were conducted to challenge the interaction between the IL-6 promoter and C/EBPβ.
View Article and Find Full Text PDFmiR‑886‑3p has been discovered to be involved in the oncogenesis, progression and metastasis of several types of human cancer. The aim of the present study was to identify the biological function of miR‑886‑3p in clear cell renal cell carcinoma (ccRCC) and to determine its possible molecular mechanisms. miR‑886‑3p was found to be significantly upregulated in ccRCC tissues (P<0.
View Article and Find Full Text PDFLong non-coding RNA urothelial carcinoma associated 1 (UCA1) was first identified in bladder cancer tissues. High expression of UCA1 in bladder cancer has suggested it may serve as a potential diagnostic molecular marker for bladder cancer. Subsequent research in bladder cancer cell lines showed that UCA1 can promote cell proliferation, but the underlying mechanism remains unknown.
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