612 results match your criteria aberrantly elevated

Upregulated Talin1 synergistically boosts β-estradiol-induced proliferation and pro-angiogenesis of eutopic and ectopic endometrial stromal cells in adenomyosis.

Reprod Biol Endocrinol 2021 May 14;19(1):70. Epub 2021 May 14.

Department of Minimally Invasive Gynecologic Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No.17 Qi Helou Road, Dong Cheng District, Beijing, 100006, China.

Adenomyosis (ADS) is an estrogen-dependent gynecological disease with unspecified etiopathogenesis. Local hyperestrogenism may serve a key role in contributing to the origin of ADS. Talin1 is mostly identified to be overexpressed and involved in the progression of numerous human carcinomas through mediating cell proliferation, adhesion and motility. Read More

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Glycosylation of Anti-Thyroglobulin IgG1 and IgG4 Subclasses in Thyroid Diseases.

Eur Thyroid J 2021 Apr 27;10(2):114-124. Epub 2020 Aug 27.

Department of Endocrinology, Peking University First Hospital, Beijing, China.

Objective: Thyroglobulin antibodies (TgAb), principally comprising immunoglobulin G (IgG), are frequently found in healthy individuals. Previously, we showed that the glycosylation levels of TgAb IgG differed across various thyroid diseases, suggesting an important role of glycosylation on antibodies in the pathogenesis of thyroid diseases. Since IgG1 and IgG4 are the primary TgAb IgG subclasses, this study aimed to investigate the glycosylation of TgAb IgG1 and IgG4 subclasses in thyroid diseases. Read More

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Disruption of FOXO3a-miRNA feedback inhibition of IGF2/IGF-1R/IRS1 signaling confers Herceptin resistance in HER2-positive breast cancer.

Nat Commun 2021 May 11;12(1):2699. Epub 2021 May 11.

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China.

Resistance to Herceptin represents a significant challenge for successful treatment of HER2-positive breast cancer. Here, we show that in Herceptin-sensitive cells, FOXO3a regulates specific miRNAs to control IGF2 and IRS1 expression, retaining basic IGF2/IGF-1R/IRS1 signaling. The basic activity maintains expression of PPP3CB, a subunit of the serine/threonine-protein phosphatase 2B, to restrict FOXO3a phosphorylation (p-FOXO3a), inducing IGF2- and IRS1-targeting miRNAs. Read More

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Hypoxic colorectal cancer-derived extracellular vesicles deliver microRNA-361-3p to facilitate cell proliferation by targeting TRAF3 via the noncanonical NF-κB pathways.

Clin Transl Med 2021 Mar;11(3):e349

Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Hypoxic tumour microenvironment (TME) is a key regulator in cancer progression. However, the communications between hypoxic cells and other components in TME during colorectal cancer (CRC) progression via extracellular vesicles (EVs) remain unclear.

Methods: High-throughput sequencing was employed to detect aberrantly expressed microRNAs (miRNAs) in hypoxic EVs. Read More

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Azathioprine antagonizes aberrantly elevated lipid metabolism and induces apoptosis in glioblastoma.

iScience 2021 Mar 26;24(3):102238. Epub 2021 Feb 26.

Drug Discovery Platform Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with poor survival rate. Temozolomide (TMZ) is used as standard chemotherapy to treat GBM, but a large number of patients either respond poorly and/or develop resistance after long-term use, emphasizing the need to develop potent drugs with novel mechanisms of action. Here, using high-throughput compound screening (HTS), we found that azathioprine, an immunosuppressant, is a promising therapeutic agent to treat TMZ-resistant GBM. Read More

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Inverse correlation of miR-27a-3p and CDH5 expression serves as a diagnostic biomarker of proliferation and metastasis of clear cell renal carcinoma.

Pathol Res Pract 2021 Apr 11;220:153393. Epub 2021 Mar 11.

Institute of Living Systems, Immanuel Kant Baltic Federal University, Kaliningrad, Russia. Electronic address:

Background: Cadherin-5 (CDH5) is aberrantly expressed in a variety of human cancers and plays an important role in angiogenesis. The present study provides further insight into the role of miR-27a-3p in the regulation of CDH5 expression in renal clear cell carcinoma (ccRCC).

Methods: Thedysregulation of CDH5 expression in ccRCC and its association with clinicopathological characteristics were analyzed using the TCGA database. Read More

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Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer.

Endocrinol Metab (Seoul) 2021 Feb 24;36(1):96-105. Epub 2021 Feb 24.

Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea.

Background: Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker. Read More

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February 2021

Long non‑coding RNA LOC284454 promotes hepatocellular carcinoma cell invasion and migration by inhibiting E‑cadherin expression.

Oncol Rep 2021 04 2;45(4). Epub 2021 Mar 2.

Department of Oncology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

Numerous studies have elucidated the impact of long non‑coding (lnc)RNAs in carcinogenesis; however, the role and the mechanism of the lncRNA LOC284454 in hepatocellular carcinoma (HCC) remain unknown. In the present study, reverse transcription‑quantitative PCR assay, χ analysis and Kaplan‑Meier analysis were performed to assess the role of LOC284454 in HCC. Furthermore, MTT and Transwell assays were performed to measure the function of LOC284454 on HCC cell proliferation, invasion and migration. Read More

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High expression of CDCA7 predicts poor prognosis for clear cell renal cell carcinoma and explores its associations with immunity.

Cancer Cell Int 2021 Mar 1;21(1):140. Epub 2021 Mar 1.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, Jiangsu Province, China.

Background: Cell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive roles of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasize its associations with immunity.

Methods: The RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Read More

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Simulated auditory fiber myelination heterogeneity desynchronizes population responses to electrical stimulation limiting inter-aural timing difference representation.

J Acoust Soc Am 2021 Feb;149(2):934

Department of Otolaryngology-Head and Neck Surgery/Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, Washington 98195-7923, USA.

Auditory nerve responses to electrical stimulation exhibit aberrantly synchronous response latencies to low-rate pulse trains, nevertheless, cochlear implant users generally have elevated inter-aural timing difference detection thresholds. These findings present an apparent paradox in which single units are unusually precise but downstream within the auditory pathway access to this precision is lost. Auditory nerves innervating a region of cochlea exhibit natural heterogeneity in their diameter, myelination, and other structural properties; a key question is whether this diversity may contribute to the loss of temporal fidelity. Read More

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February 2021

Hyperphosphatemia in chronic kidney disease exacerbates atherosclerosis via a mannosidases-mediated complex-type conversion of SCAP N-glycans.

Kidney Int 2021 Feb 23. Epub 2021 Feb 23.

John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, London, United Kingdom; Centre for Lipid Research and Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China. Electronic address:

Blood phosphate levels are linked to atherosclerotic cardiovascular disease in patients with chronic kidney disease (CKD), but the molecular mechanisms remain unclear. Emerging studies indicate an involvement of hyperphosphatemia in CKD accelerated atherogenesis through disturbed cholesterol homeostasis. Here, we investigated a potential atherogenic role of high phosphate concentrations acting through aberrant activation of sterol regulatory element-binding protein (SREBP) and cleavage-activating protein (SCAP)-SREBP2 signaling in patients with CKD, hyperphosphatemic apolipoprotein E (ApoE) knockout mice, and cultured vascular smooth muscle cells. Read More

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February 2021

Epstein-Barr Functional Mimicry: Pathogenicity of Oncogenic Latent Membrane Protein-1 in Systemic Lupus Erythematosus and Autoimmunity.

Front Immunol 2020 3;11:606936. Epub 2021 Feb 3.

Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.

Systemic lupus erythematosus (SLE) and other autoimmune diseases are propelled by immune dysregulation and pathogenic, disease-specific autoantibodies. Autoimmunity against the lupus autoantigen Sm is associated with cross-reactivity to Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1). Additionally, EBV latent membrane protein-1 (LMP1), initially noted for its oncogenic activity, is an aberrantly active functional mimic of the B cell co-stimulatory molecule CD40. Read More

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February 2021

Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy.

Blood Cancer Discov 2021 Jan 3;2(1):54-69. Epub 2020 Dec 3.

Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany.

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition. Read More

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January 2021

The double face of miR-320: cardiomyocytes-derived miR-320 deteriorated while fibroblasts-derived miR-320 protected against heart failure induced by transverse aortic constriction.

Signal Transduct Target Ther 2021 Feb 18;6(1):69. Epub 2021 Feb 18.

Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China.

MicroRNAs (miRNAs) are aberrantly expressed in the pathophysiologic process of heart failure (HF). However, the functions of a certain miRNA in different cardiac cell types during HF are scarcely reported, which might be covered by the globe effects of it on the heart. In the current study, Langendorff system was applied to isolate cardiomyocytes (CMs) and cardiac fibroblasts (CFs) from transverse aortic constriction (TAC)-induced mice. Read More

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February 2021

Novel roles of an intragenic G-quadruplex in controlling microRNA expression and cardiac function.

Nucleic Acids Res 2021 03;49(5):2522-2536

Department of Cardiology, Institute of Vascular Medicine, NHC Key Laboratory of Cardiovascular Molecular Biology and RegulatoryPeptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Third Hospital, Beijing 100191, China.

Simultaneous dysregulation of multiple microRNAs (miRs) affects various pathological pathways related to cardiac failure. In addition to being potential cardiac disease-specific markers, miR-23b/27b/24-1 were reported to be responsible for conferring cardiac pathophysiological processes. In this study, we identified a conserved guanine-rich RNA motif within the miR-23b/27b/24-1 cluster that can form an RNA G-quadruplex (rG4) in vitro and in cells. Read More

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Up-Regulation of circEIF6 Contributes to Pancreatic Cancer Development Through Targeting miR-557//PI3K/AKT Signaling.

Cancer Manag Res 2021 12;13:247-258. Epub 2021 Jan 12.

Department of Hepatobiliary Surgery, The First People's Hospital of Jingzhou, Jingzhou 434000, People's Republic of China.

Background: Accruing evidences have pointed out that abnormal expression of circular RNAs (circRNAs) was closely related to the development of many malignancies. The present study intended to disclose the role of circRNA eukaryotic translation initiation factor 6 (circEIF6; hsa_circ_0060055) in pancreatic cancer progression.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of circEIF6, messenger RNA (mRNA), microRNA-557 (miR-557) and solute carrier family 7 member 11 () mRNA. Read More

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January 2021

Efficacy of 125I seed implantation combined with intermittent hormonal therapy on moderate- and high-risk non-metastatic prostate cancer.

J BUON 2020 Nov-Dec;25(6):2616-2622

Department of Emergency and Trauma Surgery, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, China.

Purpose: Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1-214 transcript (PVT1-214) is a notable lncRNA involved in gastric cancer and colorectal cancer (CRC) so far. Nowadays, the biological function of PVT1-214 on the response of CRC to chemotherapy is still unclear. We aimed to explore the molecular mechanism of PVT1-214 and its regulatory mechanism in advanced CRC. Read More

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January 2021

Aberrant role of ALK in tau proteinopathy through autophagosomal dysregulation.

Mol Psychiatry 2021 Jan 15. Epub 2021 Jan 15.

School of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.

Proteinopathy in neurodegenerative diseases is typically characterized by deteriorating activity of specific protein aggregates. In tauopathies, including Alzheimer's disease (AD), tau protein abnormally accumulates and induces dysfunction of the affected neurons. Despite active identification of tau modifications responsible for tau aggregation, a critical modulator inducing tau proteinopathy by affecting its protein degradation flux is not known. Read More

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January 2021

Concerted roles of PTEN and ATM in controlling hematopoietic stem cell fitness and dormancy.

J Clin Invest 2021 Mar;131(5)

Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

In order to sustain proficient life-long hematopoiesis, hematopoietic stem cells (HSCs) must possess robust mechanisms to preserve their quiescence and genome integrity. DNA-damaging stress can perturb HSC homeostasis by affecting their survival, self-renewal, and differentiation. Ablation of the kinase ataxia telangiectasia mutated (ATM), a master regulator of the DNA damage response, impairs HSC fitness. Read More

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Diagnostic and Prognostic Significance of Dysregulated Expression of Circular RNAs in Osteosarcoma.

Expert Rev Mol Diagn 2021 Feb 22;21(2):235-244. Epub 2021 Jan 22.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Objective: This study aimed to perform an updated meta-analysis to explore the clinical, diagnostic, and prognostic values of circRNAs in osteosarcoma.

Methods: : PubMed, Web of Science, EMBASE, Scopus, and Cochrane Library were systematically searched up to December 15, 2020. Eligible studies regarding the relationship between circRNAs levels and clinicopathological, diagnostic, and prognostic values in osteosarcoma were included for study. Read More

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February 2021

Persistently Elevated mTOR Complex 1-S6 Kinase 1 Disrupts DARPP-32-Dependent D Dopamine Receptor Signaling and Behaviors.

Biol Psychiatry 2020 Oct 27. Epub 2020 Oct 27.

Solomon Snyder Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. Electronic address:

Background: The serine-threonine kinase mTORC1 (mammalian target of rapamycin complex 1) is essential for normal cell function but is aberrantly activated in the brain in both genetic-developmental and sporadic diseases and is associated with a spectrum of neuropsychiatric symptoms. The underlying molecular mechanisms of cognitive and neuropsychiatric symptoms remain controversial.

Methods: The present study examines behaviors in transgenic models that express Rheb, the most proximal known activator of mTORC1, and profiles striatal phosphoproteomics in a model with persistently elevated mTORC1 signaling. Read More

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October 2020

Elevated serum miR-3129-5p contributes to the progression of coronary heart disease via targeting mTOR.

Kaohsiung J Med Sci 2021 Apr 18;37(4):314-323. Epub 2020 Dec 18.

Department of Cardiology, Affiliated Hospital of Yan'an University, China.

The current study aims to explore the miRNA changes that occur in the serum of patients with coronary heart disease (CHD) and healthy controls using a microarray technique, thereby exploring the potential biomarkers in the diagnosis of CHD and the underlying mechanism. Clinical data were reviewed, and venous blood samples were collected from 66 cases of CHD and 58 cases of healthy controls. MicroRNA-wide expression profiling identified 16 miRNAs that were aberrantly decreased by ~2-fold in the serum of patients with CHD compared to that of healthy controls. Read More

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Defective FXR-SHP Regulation in Obesity Aberrantly Increases Expression, Promoting Insulin Resistance and Fatty Liver.

Diabetes 2021 Mar 16;70(3):733-744. Epub 2020 Dec 16.

Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL

Aberrantly elevated expression in obesity of microRNAs (miRNAs), including the miRNA miR-802, contributes to obesity-associated metabolic complications, but the mechanisms underlying the elevated expression are unclear. Farnesoid X receptor (FXR), a key regulator of hepatic energy metabolism, has potential for treatment of obesity-related diseases. We examined whether a nuclear receptor cascade involving FXR and FXR-induced small heterodimer partner (SHP) regulates expression of to maintain glucose and lipid homeostasis. Read More

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Costameric integrin and sarcoglycan protein levels are altered in a model for Limb-girdle muscular dystrophy type 2H.

Mol Biol Cell 2021 02 9;32(3):260-273. Epub 2020 Dec 9.

Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506.

Mutations in two different domains of the ubiquitously expressed TRIM32 protein give rise to two clinically separate diseases, one of which is Limb-girdle muscular dystrophy type 2H (LGMD2H). Uncovering the muscle-specific role of TRIM32 in LGMD2H pathogenesis has proven difficult, as neurogenic phenotypes, independent of LGMD2H pathology, are present in mice. We previously established a platform to study LGMD2H pathogenesis using as a model. Read More

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February 2021

GATA6 activated long non-coding RNA PCAT1 maintains stemness of non-small cell lung cancer by mediating FRK.

J BUON 2020 Sep-Oct;25(5):2371-2381

Department of Cardiothoracic Surgery, Suqian First Hospital, Suquian 223 800, China.

Purpose: Long non-coding RNA (lncRNA) prostate cancer-associated transcripts 1 (PCAT1) is a noticeable lncRNA involved in the tumorigenesis of various cancers. Nowadays, the biological function of PCAT1 on the stemness of non-small cell lung cancer (NSCLC) is still unclear. Our purpose was to explore the molecular mechanism of PCAT1 and its target protein in advanced NSCLC. Read More

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December 2020

IRF-1 mediated long non-coding RNA PVT1-214 promotes oxaliplatin resistance of colorectal cancer via miR-128 inhibition.

J BUON 2020 Sep-Oct;25(5):2205-2214

Department of Oncology, 970th Hospital of the PLA Joint Logistics Support Force, no. 7 Zhichu South Rd, Yantai 264000, China.

Purpose: Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1-214 transcript (PVT1-214) is a notable lncRNA involved in gastric cancer and colorectal cancer (CRC) so far. Nowadays, the biological function of PVT1-214 on the response of CRC to chemotherapy is still unclear. We aimed to explore the molecular mechanism of PVT1-214 and its regulatory mechanism in advanced CRC. Read More

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December 2020

p38γ Activation and BGP (Biliary Glycoprotein) Induction in Primates at Risk for Inflammatory Bowel Disease and Colorectal Cancer-A Comparative Study with Humans.

Vaccines (Basel) 2020 Dec 2;8(4). Epub 2020 Dec 2.

Research and Development Service, Department of Internal Medicine, Detroit VAMC, Detroit, MI 48201, USA.

Colorectal cancer (CRC) is a common cause of cancer-related deaths largely due to CRC liver metastasis (CRLM). Identification of targetable mechanisms continues and includes investigations into the role of inflammatory pathways. Of interest, MAPK is aberrantly expressed in CRC patients, yet the activation status is not defined. Read More

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December 2020

KIAA1429 promotes the progression of lung adenocarcinoma by regulating the m6A level of MUC3A.

Pathol Res Pract 2021 Jan 12;217:153284. Epub 2020 Nov 12.

Research Department, Affiliated Tumor Hospital of Guangxi Medical University, PR China. Electronic address:

Objective: Lung adenocarcinoma (LUAD) is one of the most frequently occurring human malignancies worldwide, but its potential molecular mechanism has not yet been fully elucidated. N6-methyladenosine (m6A), the most common internal chemical modification of mRNAs, is implicated in diverse pathological processes in different human malignancies, but its functions in LUAD remain elusive. The current study aimed to investigate the function and molecular mechanism of KIAA1429 in LUAD. Read More

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January 2021

Intestinal FGF15/19 physiologically repress hepatic lipogenesis in the late fed-state by activating SHP and DNMT3A.

Nat Commun 2020 11 24;11(1):5969. Epub 2020 Nov 24.

Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.

Hepatic lipogenesis is normally tightly regulated but is aberrantly elevated in obesity. Fibroblast Growth Factor-15/19 (mouse FGF15, human FGF19) are bile acid-induced late fed-state gut hormones that decrease hepatic lipid levels by unclear mechanisms. We show that FGF15/19 and FGF15/19-activated Small Heterodimer Partner (SHP/NR0B2) have a role in transcriptional repression of lipogenesis. Read More

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November 2020

WNT4 secreted by tumor tissues promotes tumor progression in colorectal cancer by activation of the Wnt/β-catenin signalling pathway.

J Exp Clin Cancer Res 2020 Nov 23;39(1):251. Epub 2020 Nov 23.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

Background: Wingless and Int-related protein (Wnt) ligands are aberrantly expressed in patients with colorectal cancer (CRC). However, the aberrant level of Wnt ligands in serum have not been explored. Here, we aimed to identify the levels of WNT4 in serum and explored its oncogenic role in CRC. Read More

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November 2020