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Bioscience Reports Jan 2022Acute pulmonary embolism (APE) is a prevalent reason of cardiovascular morbidity and mortality. Recent studies have underscored the positive effects of microRNAs...
BACKGROUND
Acute pulmonary embolism (APE) is a prevalent reason of cardiovascular morbidity and mortality. Recent studies have underscored the positive effects of microRNAs (miRNAs) on many diseases. The present study aimed to identify the critical miRNA with differential expressions and explore its role in APE.
METHODS
The critical miRNA with its target gene was screened by bioinformatics analysis. Their binding relationship was analyzed by TargetScan, Dual-luciferase reporter and RNA pull-down assays. A rat model of APE was established by self-blood coagulum. Human pulmonary artery smooth muscle cells (PASMCs) were exposed to platelet-derived growth factor (PDGF-BB) for excessive proliferation, and transfected with miR-34a-3p mimic. Mean pulmonary arterial pressure (mPAP) of rat was measured, and the pulmonary tissues were used for the pathological observation by Hematoxylin-Eosin (H&E) staining. Cell viability and proliferation were detected by Cell Counting Kit-8 (CCK-8) and EdU assays. The expressions of miR-34a-3p with its target genes (including dual-specificity phosphatase-1 (DUSP1)), neuron-derived orphan receptor-1 (NOR-1) and proliferating cell nuclear antigen (PCNA) were determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR) or/and Western blot.
RESULTS
MiR-34a-3p expression was down-regulated in APE patients, which attenuated the increment of mPAP and thickening of the pulmonary arterial walls in APE rats, accompanied with regulation of NOR-1 and PCNA levels. MiR-34a-3p suppressed DUSP1 expression by directly binding to its 3'-untranslated region (UTR), and attenuated cell viability, proliferation, and the expressions of NOR-1 and PCNA in PDGF-BB-induced PASMCs by inhibiting DUSP1 expression.
CONCLUSION
Up-regulated miR-34a-3p negatively regulates DUSP1 expression to inhibit PASMC proliferation, which, thus, may act on APE treatment by negatively regulating pulmonary vascular proliferation.
Topics: Animals; Case-Control Studies; Cell Proliferation; Cells, Cultured; DNA-Binding Proteins; Disease Models, Animal; Dual Specificity Phosphatase 1; Gene Expression Regulation, Enzymologic; Male; Membrane Transport Proteins; MicroRNAs; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nerve Tissue Proteins; Proliferating Cell Nuclear Antigen; Pulmonary Artery; Pulmonary Embolism; Rats, Sprague-Dawley; Signal Transduction; Vascular Remodeling; Rats
PubMed: 34778900
DOI: 10.1042/BSR20210116 -
Indian Journal of Dermatology,... 2023Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum.
BACKGROUND
Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum.
AIMS
This study aimed to evaluate the spectrum and pathogenesis of contiguous squamous proliferation in syringocystadenoma papilliferum.
MATERIALS AND METHODS
All cases of syringocystadenoma papilliferum diagnosed over the past 12 years were screened for contiguous squamous proliferation. Cases with associated nevus sebaceous were excluded from the study. Immunohistochemistry for GATA3, CK7, BRAFV600E and p16 was performed. PCR for human papilloma virus, type 16 and 18, was carried out.
RESULTS
Of a total of 30 cases, 14 cases showed associated contiguous squamous proliferation which included four cases of verrucous hyperplasia, six cases with papillomatosis, two cases with mild squamous hyperplasia and one case each of Bowen's disease and squamous cell carcinoma. In the cases with non-neoplastic contiguous squamous proliferations, the squamous component did not express CK7 or GATA3. However, the squamous component of premalignant and malignant lesions expressed CK7 and GATA3 concordant with the adenomatous component. BRAF was positive in adenomatous component in five cases while the contiguous squamous proliferation component was negative for BRAF in all but one case. p16 was negative in both components of all cases and PCR for human papilloma virus was negative in all cases.
LIMITATIONS
Due to the rarity of disease, the sample size of our study was relatively small with two cases in the 2nd group, that is, syringocystadenoma papilliferum with malignant contiguous squamous proliferation. Detailed molecular studies such as gene sequencing were not performed.
CONCLUSION
Syringocystadenoma papilliferum with contiguous squamous proliferation is underreported, and most commonly displays verrucous hyperplasia. The premalignant and malignant contiguous squamous proliferations likely arise from syringocystadenoma papilliferum while the hyperplastic contiguous squamous proliferations likely arise from the adjacent epidermis. Relationship with high-risk human papilloma virus is unlikely. However, further molecular analysis of larger number of cases is required to establish the pathogenesis.
Topics: Humans; Tubular Sweat Gland Adenomas; Sweat Gland Neoplasms; Retrospective Studies; Proto-Oncogene Proteins B-raf; Hyperplasia; Carcinoma, Squamous Cell
PubMed: 34623039
DOI: 10.25259/IJDVL_845_20 -
Circulation Jun 2024Endothelial cell (EC) apoptosis and proliferation of apoptosis-resistant cells is a hallmark of pulmonary hypertension (PH). Yet, why some ECs die and others proliferate...
BACKGROUND
Endothelial cell (EC) apoptosis and proliferation of apoptosis-resistant cells is a hallmark of pulmonary hypertension (PH). Yet, why some ECs die and others proliferate and how this contributes to vascular remodeling is unclear. We hypothesized that this differential response may: (1) relate to different EC subsets, namely pulmonary artery (PAECs) versus microvascular ECs (MVECs); (2) be attributable to autophagic activation in both EC subtypes; and (3) cause replacement of MVECs by PAECs with subsequent distal vessel muscularization.
METHODS
EC subset responses to chronic hypoxia were assessed by single-cell RNA sequencing of murine lungs. Proliferative versus apoptotic responses, activation, and role of autophagy were assessed in human and rat PAECs and MVECs, and in precision-cut lung slices of wild-type mice or mice with endothelial deficiency in the autophagy gene (). Abundance of PAECs versus MVECs in precapillary microvessels was assessed in lung tissue from patients with PH and animal models on the basis of structural or surface markers.
RESULTS
In vitro and in vivo, PAECs proliferated in response to hypoxia, whereas MVECs underwent apoptosis. Single-cell RNA sequencing analyses support these findings in that hypoxia induced an antiapoptotic, proliferative phenotype in arterial ECs, whereas capillary ECs showed a propensity for cell death. These distinct responses were prevented in hypoxic mice or after silencing, yet replicated by autophagy stimulation. In lung tissue from mice, rats, or patients with PH, the abundance of PAECs in precapillary arterioles was increased, and that of MVECs reduced relative to controls, indicating replacement of microvascular by macrovascular ECs. EC replacement was prevented by genetic or pharmacological inhibition of autophagy in vivo. Conditioned medium from hypoxic PAECs yet not MVECs promoted pulmonary artery smooth muscle cell proliferation and migration in a platelet-derived growth factor-dependent manner. Autophagy inhibition attenuated PH development and distal vessel muscularization in preclinical models.
CONCLUSIONS
Autophagic activation by hypoxia induces in parallel PAEC proliferation and MVEC apoptosis. These differential responses cause a progressive replacement of MVECs by PAECs in precapillary pulmonary arterioles, thus providing a macrovascular context that in turn promotes pulmonary artery smooth muscle cell proliferation and migration, ultimately driving distal vessel muscularization and the development of PH.
PubMed: 38873770
DOI: 10.1161/CIRCULATIONAHA.124.068726 -
Journal of Clinical Laboratory Analysis Aug 2022Serous ovarian carcinoma (SOC) is a common malignant tumor in female reproductive system. Long noncoding RNA (lncRNA) LIFR-AS1 is a tumor suppressor gene in colorectal...
BACKGROUND
Serous ovarian carcinoma (SOC) is a common malignant tumor in female reproductive system. Long noncoding RNA (lncRNA) LIFR-AS1 is a tumor suppressor gene in colorectal cancer, but its effect and underlying mechanism in SOC are still unclear. Therefore, this study focuses on unveiling the regulatory mechanism of LIFR-AS1 in SOC.
METHODS
The relationship between LIFR-AS1 expression and prognosis of SOC patients was analyzed by TCGA database and Starbase, and then, the LIFR-AS1 expression in SOC tissues and cells was detected by quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Besides, the relationship between LIFR-AS1 and clinical characteristics was analyzed. Also, the effects of LIFR-AS1 on the biological behaviors of SOC cells were measured by Cell Counting Kit-8, colony formation, and wound-healing and Transwell assays, respectively. Western blot and qRT-PCR were employed to determine the protein expressions of genes related to proliferation (PCNA), apoptosis (cleaved caspase-3), epithelial-mesenchymal transition (E-cadherin, N-cadherin, and Snail).
RESULTS
LIFR-AS1 was lowly expressed in SOC, which was correlated with the poor prognosis of SOC patients. Low expression of LIFR-AS1 in SOC was associated with the tumor size, clinical stage, lymph node metastasis, and distant metastasis. LIFR-AS1 overexpression promoted the expressions of cleaved caspase-3 and E-cadherin while suppressing the malignant behaviors (proliferation, migration, and invasion) of SOC cells, the expressions of PCNA, N-cadherin, and Snail. Besides, silencing LIFR-AS1 exerted the effects opposite to overexpressed LIFR-AS1.
CONCLUSION
LIFR-AS1 overexpression inhibits biological behaviors of SOC cells, which may be a new therapeutic method.
Topics: Cadherins; Carcinoma, Ovarian Epithelial; Caspase 3; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Humans; Leukemia Inhibitory Factor Receptor alpha Subunit; Ovarian Neoplasms; Proliferating Cell Nuclear Antigen; RNA, Long Noncoding
PubMed: 35778954
DOI: 10.1002/jcla.24570 -
European Journal of Histochemistry : EJH Oct 2023Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways....
Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways. The cocaine-amphetamine-regulated-transcript (CART) peptide has several physiological functions, and it is widely expressed in several organs. CART increases the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor (BDNF), whose expression has been correlated to the proliferation rate of cholangiocytes. In the present study, we aimed to evaluate the expression of CART and its role in modulating cholangiocyte proliferation in healthy and bile duct ligated (BDL) rats in vivo, as well as in cultured normal rat cholangiocytes (NRC) in vitro. Liver samples from both healthy and BDL (1 week) rats, were analyzed by immunohistochemistry and immunofluorescence for CART, CK19, TrkB and p75NTR BDNF receptors. PCNA staining was used to evaluate the proliferation of the cholangiocytes, whereas TUNEL assay was used to evaluate biliary apoptosis. NRC treated or not with CART were used to confirm the role of CART on cholangiocytes proliferation and the secretion of BDNF. Cholangiocytes proliferation, apoptosis, CART and TrkB expression were increased in BDL rats, compared to control rats. We found a higher expression of TrkB and p75NTR, which could be correlated with the proliferation rate of biliary tree during BDL. The in vitro study demonstrated increased BDNF secretion by NRC after treatment with CART compared with control cells. As previously reported, proliferating cholangiocytes acquire a neuroendocrine phenotype, modulated by several factors, including neurotrophins. Accordingly, CART may play a key role in the remodeling of biliary epithelium during cholestasis by modulating the secretion of BDNF.
Topics: Animals; Rats; Bile Ducts; Brain-Derived Neurotrophic Factor; Cell Proliferation; Epithelium; Nerve Tissue Proteins
PubMed: 37859350
DOI: 10.4081/ejh.2023.3846 -
Molecular Medicine Reports May 2023Nasopharyngeal carcinoma (NPC) is a primary malignancy that originates from the nasopharyngeal region. It has been demonstrated that a decrease in the expression level...
Nasopharyngeal carcinoma (NPC) is a primary malignancy that originates from the nasopharyngeal region. It has been demonstrated that a decrease in the expression level of cell division cycle gene 25A (CDC25A) suppresses cell viability and induces apoptosis in a variety of different types of cancer. However, at present, the role of CDC25A in NPC has yet to be fully elucidated. Therefore, the aim of the present study was to investigate the role of CDC25A in NPC progression and to explore the potential underlying mechanism. Reverse transcription‑quantitative PCR was performed to detect the relative mRNA levels of CDC25A and E2F transcription factor 1 (E2F1). Western blot analysis was subsequently used to determine the expression levels of CDC25A, Ki67, proliferating cell nuclear antigen (PCNA) and E2F1. CCK8 assay was employed to measure cell viability and flow cytometric analysis was employed to analyze the cell cycle. The binding sites between the CDC25A promoter and E2F1 were predicted using bioinformatics tools. Finally, luciferase reporter gene and chromatin immunoprecipitation assays were performed to verify the interaction between CDC25A and E2F1. The results obtained suggested that CDC25A is highly expressed in NPC cell lines and CDC25A silencing was found to inhibit cell proliferation, reduce the protein expression levels of Ki67 and PCNA and induce G1 arrest of NPC cells. Furthermore, E2F1 could bind CDC25A and positively regulate its expression at the transcriptional level. In addition, CDC25A silencing abolished the effects of E2F1 overexpression on cell proliferation and the cell cycle in NPC. Taken together, the findings of the present study showed that CDC25A silencing attenuated cell proliferation and induced cell cycle arrest in NPC and CDC25A was regulated by E2F1. Hence, CDC25A may be a promising therapeutic target for treatment of NPC.
Topics: Humans; Nasopharyngeal Carcinoma; Proliferating Cell Nuclear Antigen; Genes, cdc; Ki-67 Antigen; Cell Line, Tumor; Cell Proliferation; Cell Cycle Checkpoints; Cell Cycle; Nasopharyngeal Neoplasms; Gene Expression Regulation, Neoplastic; cdc25 Phosphatases
PubMed: 37052240
DOI: 10.3892/mmr.2023.12996 -
JCI Insight Dec 2020Cardiac fibrosis is a pathophysiologic hallmark of the aging heart, but little is known about how fibroblast proliferation and transcriptional programs change throughout...
Cardiac fibrosis is a pathophysiologic hallmark of the aging heart, but little is known about how fibroblast proliferation and transcriptional programs change throughout the life span of the organism. Using EdU pulse labeling, we demonstrated that more than 50% of cardiac fibroblasts were actively proliferating in the first day of postnatal life. However, by 4 weeks, only 10% of cardiac fibroblasts were proliferating. By early adulthood, the fraction of proliferating cardiac fibroblasts further decreased to approximately 2%, where it remained throughout the rest of the organism's life. We observed that maximal changes in cardiac fibroblast transcriptional programs and, in particular, collagen and ECM gene expression both in the heart and cardiac fibroblast were maximal in the newly born and juvenile animal and decreased with organismal aging. Examination of DNA methylation changes both in the heart and in cardiac fibroblasts did not demonstrate significant changes in differentially methylated regions between young and old mice. Our observations demonstrate that cardiac fibroblasts attain a stable proliferation rate and transcriptional program early in the life span of the organism and suggest that phenotypic changes in the aging heart are not directly attributable to changes in proliferation rate or altered collagen expression in cardiac fibroblasts.
Topics: Age Factors; Animals; Cell Proliferation; Cells, Cultured; Collagen; Collagen Type I; Extracellular Matrix; Fibroblasts; Fibrosis; Gene Expression; Gene Expression Regulation; Heart; Mice; Mice, Inbred C57BL; Myocardium
PubMed: 33180747
DOI: 10.1172/jci.insight.140628 -
Animals : An Open Access Journal From... Jul 2022The E2F family of transcription factor is divided into activators and repressors that control cell proliferation. Bovine mammary epithelial cells (BMECs) can be...
The E2F family of transcription factor is divided into activators and repressors that control cell proliferation. Bovine mammary epithelial cells (BMECs) can be immortalized using human papillomavirus 16 E6E7 (HPV16 E6E7) and simian vacuolating virus 40 large T antigen (SV40T). In addition, SV40T does not require E2F1, E2F2, and E2F3 activators to induce proliferation in mouse embryo fibroblasts (MEFs). However, we report that E2F3 activator is required to induce the proliferation of BMECs. Our results showed that, at an early stage, primary BMECs lacking the E2F1 expression have the capacity to proliferate and show E2F2 and E2F3 slight protein levels. At a late stage, primary BMECs deficient for E2F3 completely abolish any proliferative ability and exhibit a severe cell senescence signal, although the E2F2 can be expressed at a late stage of primary BMECs. Compared with the late stage of primary BMECs, the BMECs immortalized by SV40T and E6E7 restored the protein level of E2F3 and enhanced the CDK4, CDK6, cyclin D3, and CDK2 protein level, leading to proliferating robustly. Surprisingly, it was found that p53, p21, and p27 were upregulated in SV40T and E6E7-immortalized BMECs, relatively to primary BMECs. Notably, Cdc2 was almost expressed in primary BMECs. However, Cdc2 was elevated in BMECs immortalized by SV40T and E6E7. In conclusion, this study revealed a molecular mechanism where E2F3 controls the BMECs' proliferation and senescence.
PubMed: 35883337
DOI: 10.3390/ani12141790 -
Faculty Reviews 2023Cell proliferation control is essential during development and for maintaining adult tissues. Loss of that control promotes not only oncogenesis when cells proliferate... (Review)
Review
Cell proliferation control is essential during development and for maintaining adult tissues. Loss of that control promotes not only oncogenesis when cells proliferate inappropriately but also developmental abnormalities or degeneration when cells fail to proliferate when and where needed. To ensure that cells are produced at the right place and time, an intricate balance of pro-proliferative and anti-proliferative signals impacts the probability that cells undergo cell cycle exit to quiescence, or G phase. This brief review describes recent advances in our understanding of how and when quiescence is initiated and maintained in mammalian cells. We highlight the growing appreciation for quiescence as a collection of context-dependent distinct states.
PubMed: 36923701
DOI: 10.12703/r/12-5 -
LINC00106/RPS19BP1/p53 axis promotes the proliferation and migration of human prostate cancer cells.PeerJ 2023Prostate cancer (PCa) is among the most prevalent cancers in males with high biochemical recurrence risk. LINC00106 contributes to the carcinogenesis of Hepatocellular...
BACKGROUND
Prostate cancer (PCa) is among the most prevalent cancers in males with high biochemical recurrence risk. LINC00106 contributes to the carcinogenesis of Hepatocellular carcinoma (HCC). However, it is unclear how it affects PCa advancement. Here, we studied LINC00106's effects on PCa cells' ability to proliferate, invade, and metastasize.
METHODS
The data of LINC00106 from The Cancer Genome Atlas (TCGA) in human PCa tissues were analyzed using TANRIC and survival analysis. In order to determine the expression levels of genes and proteins, we also performed reverse transcription-quantitative PCR and western blot analysis. The migration, invasion, colony formation, and proliferation (CCK-8) of PCa cells with LINC00106 knockdown were investigated. The impact of LINC00106 on cell proliferation and invasion was also analyzed in mice. LncRNA prediction software catRAPID omics v2.1 (catRAPID omics v2.0 (tartaglialab.com)) was used to predict proteins that might interact with LINC00106. The interactions were verified via RNA immunoprecipitation and RNA pull-down assays and finally, the interaction between LINC00106 and its target protein and the p53 signaling pathway was studied using a dual-luciferase reporter assay.
RESULTS
In PCa, LINC00106 was over-expressed in comparison to normal tissues, and it was linked to an unfavorableprognosis. and analyses showed that downregulating LINC00106 decreased PCa cells'ability to proliferate and migrate. A common regulatory axis generated by LINC00106 and RPS19BP1 prevents p53 activity.
CONCLUSION
Our experimental data indicate that LINC00106 functions as an oncogene in the onset of PCa, and the LINC00106/RPS19BP1/P53 axis canserve as a novel therapeutic target for PCa treatment.
Topics: Male; Humans; Animals; Mice; Tumor Suppressor Protein p53; Carcinoma, Hepatocellular; Liver Neoplasms; Prostatic Neoplasms; MicroRNAs; Cell Proliferation
PubMed: 37180577
DOI: 10.7717/peerj.15232