The Tohoku journal of experimental medicine
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Tohoku J. Exp. Med. · Jun 2022
Long Noncoding RNA Solute Carrier Family 25 Member 21 Antisense RNA 1 Inhibits Cell Malignant Behaviors and Enhances Radiosensitivity of Gastric Cancer Cells by Upregulating Synuclein Gamma Expression.
Long noncoding RNAs (LncRNAs) were reported to be implicated in the progression of gastric cancer (GC). This study aimed to explore the role of solute carrier family 25 member 21 antisense RNA 1 (SLC25A21-AS1) in radiosensitivity of GC cells. In the present study, reverse transcription quantitative polymerase chain reaction (RT-qPCR) showed that the expression of SLC25A21-AS1 and synuclein gamma (SNCG) was downregulated in GC tissues and cells, while the expression of microRNA-15a-5p (miR-15a-5p) was upregulated in GC tissues and cells. ⋯ Rescue assays revealed that SNCG silencing rescued the tumor-suppressive effect of overexpressed SLC25A21-AS1 on GC cells. The enhanced radiosensitivity caused by SLC25A21-AS1 overexpression was also reduced by SNCG knockdown. In conclusion, lncRNA SLC25A21-AS1 inhibits cell malignant behaviors and enhances cell radiosensitivity in GC by elevating SNCG expression.
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Tohoku J. Exp. Med. · Jun 2022
Prevalence of Psoriatic Arthritis in Nagano Prefecture, Japan, and Efficacy of the Psoriasis Epidemiology Screening Tool: A Real-World Survey.
Pain, stiffness, and swelling are the main joint symptoms of psoriatic arthritis (PsA); however, they are also common symptoms of other joint diseases. Therefore, it is challenging to distinguish PsA from other joint diseases. To evaluate the prevalence of PsA and the frequency of joint symptoms in psoriasis patients, we conducted a prefecture-wide survey using the Psoriasis Epidemiology Screening Tool (PEST), a patient questionnaire for screening PsA to assess joint symptoms. ⋯ This may have been due to the enrollment of a large number of patients treated in clinics. Many patients with PsA were treated at hospitals, which likely reflects the tendency of patients with joint symptoms to receive intensive treatment in hospitals. In addition, based on the lower sensitivity of the PEST in this study, further studies are necessary to establish the validity of the PEST.
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Tohoku J. Exp. Med. · Jun 2022
TM5614, an Inhibitor of Plasminogen Activator Inhibitor-1, Exerts an Antitumor Effect on Chronic Myeloid Leukemia.
Chronic myeloid leukemia (CML) is triggered by t(9;22)(q34;q11.2) translocation, leading to the formation of the BCR-ABL1 fusion gene. Although the development of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has dramatically improved the prognosis of CML, the disease could often relapse, presumably because leukemic stem cell fraction of CML (CML-LSC) may reside in specific niches, and also acquire an ability to resist the cytotoxic agents. Recently a study indicated that pharmacological inhibition of plasminogen activator inhibitor-1 (PAI-1, also known as SERPINE1) would cause detachment of CML-LSCs from their niche by inducing maturation of membrane-type matrix metalloprotease-1 (MT1-MMP), leading to increased susceptibility of CML-LSCs against TKIs. ⋯ In K562/PAI-1 cells, TM5614 treatment increased NOTCH1 intracellular domain (NICD) protein expression as well as NOTCH1 target of HEY1 mRNA levels. Finally, forced expression of either Furin or NICD in K562/PAI-1 cells significantly inhibited cell proliferation and induced apoptosis. Collectively, PAI-1 inhibition may have an antitumor effect by modulating the Furin/NICD pathway.
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Tohoku J. Exp. Med. · Jun 2022
Co-localization of Fibronectin Receptors LILRB4/gp49B and Integrin on Dendritic Cell Surface.
A myeloid immune checkpoint, leukocyte immunoglobulin-like receptor (LILR) B4 (B4, also known as ILT3/CD85k in humans and gp49B in mice) is expressed on dendritic cells (DCs). However, a mode of regulation of DCs by B4/gp49B is not identified yet in relation to the ligand(s) as well as to the counteracting, activation-type receptor. Our recent identification of the physiological/pathological ligand for B4/gp49B as the fibronectin (FN) N-terminal 30-kDa domain poses the question of the relationship between B4/gp49B and a classical FN receptor/cellular activator, integrin, on DCs. ⋯ In the absence of gp49B, while the FAK phosphorylation level was virtually unchanged, that of phosphorylation of Syk was markedly augmented. These results suggested that the immobilized FN induced a crosstalk between gp49B and integrin in terms of the intracellular signaling of BMDCs, in which gp49B suppressed the integrin-mediated pro-inflammatory cascade. Our observations may provide a clue for elucidating the mechanism of the therapeutic efficacy of B4/gp49B blocking in autoimmune disease and cancer.
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Tohoku J. Exp. Med. · Jun 2022
The Importance of Tumor Necrosis Factor-α-Induced Protein-8 Like-2 in the Pathogenesis of Cervical Cancer and Preeclampsia via Regulation of Cell Invasion.
Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) as a novel negative immune regulator plays an important role in several human diseases. However, its influences in cervical cancer and preeclampsia (PE) remain unclear. This study aims to explore the important role of TIPE2 in cervical cancer and PE via regulating cell invasion. ⋯ Ad-TIPE2 decreased the volume and weight of xenograft tumors in the nude mice, with the down-regulation of Ki67. The quantity of cells (HTR8/SVneo and JEG3 cells) transfected with Ad-TIPE2 had increased, with up-regulations of TIPE2, matrix metalloproteinase (MMP)-2 and MMP-9. TIPE2 overexpression could reduce the invasion and migration of cervical cancer cells via inhibiting the epithelial-mesenchymal transition (EMT) process, and promote trophocyte invasion via upregulating the expression of MMPs, and it may be used as a potential therapeutic target for cervical cancer and PE.